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Quaking isoforms cooperate to promote the mesenchymal phenotype. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-29 Daniel P Neumann,Caroline A Phillips,Rachael Lumb,Helen M Palethorpe,Yesha Ramani,Brett G Hollier,Luke A Selth,Cameron P Bracken,Gregory J Goodall,Philip A Gregory
The RNA-binding protein Quaking (QKI) has widespread effects on mRNA regulation including alternative splicing, stability, translation, and localization of target mRNAs. Recently, QKI was found to be induced during epithelial-mesenchymal transition (EMT), where it promotes a mesenchymal alternative splicing signature that contributes to the mesenchymal phenotype. QKI is itself alternatively spliced
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Mechanisms underlying Myosin 10's contribution to the maintenance of mitotic spindle bipolarity. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-29 Yang-In Yim,Antonio Pedrosa,Xufeng Wu,Krishna Chinthalapudi,Richard E Cheney,John A Hammer
Myosin 10 (Myo10) couples microtubules and integrin-based adhesions to movement along actin filaments via its microtubule-binding MyTH4 domain and integrin-binding FERM domain, respectively. Here we show that Myo10 depleted HeLa cells and mouse embryo fibroblasts (MEFs) both exhibit a pronounced increase in the frequency of multipolar spindles. Staining of unsynchronized metaphase cells showed that
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LGN loss randomizes spindle orientation and accelerates tumorigenesis in PTEN-deficient epidermis. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-22 Sophie Viala,Charlotte Hadjadj,Vandana Nathan,Marie-Christine Guiot,Luke McCaffrey,Katie Cockburn,Maxime Bouchard
Loss of cell polarity and disruption of tissue organization are key features of tumorigenesis that are intrinsically linked to spindle orientation. Epithelial tumors are often characterized by spindle orientation defects, but how these defects impact tumor formation driven by common oncogenic mutations is not fully understood. Here, we examine the role of spindle orientation in adult epidermis by deleting
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Excess Phosphoserine-129 α-Synuclein Induces Synaptic Vesicle Trafficking and Declustering Defects at a Vertebrate Synapse. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-22 Jaqulin N Wallace,Zachary C Crockford,Cristina Román-Vendrell,Emily B Brady,Christian Hoffmann,Karina J Vargas,Mariana Potcoava,M Elizabeth Wegman,Simon T Alford,Dragomir Milovanovic,Jennifer R Morgan
α-Synuclein is a presynaptic protein that regulates synaptic vesicle (SV) trafficking. In Parkinson's disease (PD) and dementia with Lewy bodies (DLB), α-synuclein aberrantly accumulates throughout neurons, including at synapses. During neuronal activity, α-synuclein is reversibly phosphorylated at serine 129 (pS129). While pS129 comprises ∼4% of total α-synuclein under physiological conditions, it
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Branched microtubule nucleation and dynein transport organize RanGTP asters in Xenopus laevis egg extract. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-22 Jacopo Scrofani,Felix Ruhnow,Wei-Xiang Chew,Davide Normanno,Francois Nedelec,Thomas Surrey,Isabelle Vernos
Chromosome segregation relies on the correct assembly of a bipolar spindle. Spindle pole self-organization requires dynein-dependent microtubule transport along other microtubules. However, during M-phase RanGTP triggers microtubule nucleation and branching generating polarized arrays with non-astral organization in which microtubule minus ends are linked to the sides of other microtubules. This raises
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Inhibition of the Chromatin Remodeling Factor NURF Rescued Sterility by a Clinic Variant of NuRD. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-08 Zijie Shen,Zhengyang Guo,Guangshuo Ou,Wei Li
The nucleosome remodeling and deacetylase (NuRD) complex is essential for gene expression and cell fate determination, and missense mutations of NuRD caused neurodevelopmental diseases. However, the molecular pathogenesis of clinic NuRD variants is unknown. Here, we introduced a clinic CHD3(L915F) variant into C. elegans homolog LET-418, impairing germline and vulva development and ultimately causing
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Yeast Rim11 kinase responds to glutathione-induced stress by regulating the transcription of phospholipid biosynthetic genes. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-08 Taishi Yasukawa,Ryo Iwama,Yuriko Yamasaki,Naohisa Masuo,Yoichi Noda
Glutathione (GSH), a tripeptide composed of glycine, cysteine, and glutamic acid, is an abundant thiol found in a wide variety of cells, ranging from bacterial to mammalian cells. Adequate levels of GSH are essential for maintaining iron homeostasis. The ratio of oxidized/reduced GSH is strictly regulated in each organelle to maintain the cellular redox potential. Cellular redox imbalances cause defects
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CDK signaling via nonconventional CDK phosphorylation sites. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-01 Ervin Valk,Mihkel Örd,Ilona Faustova,Mart Loog
Since the discovery of cyclin-dependent kinases (CDKs), it has been perceived as a dogma that CDK signaling in the cell cycle is mediated via targeting the CDK consensus sites: the optimal and the minimal motifs S/T-P-x-K/R and S/T-P, respectively. However, more recent evidence suggests that often the CDK phosphorylation events of regulatory importance are mediated via nonconventional CDK sites that
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The evolution and diversity of actin-dependent cell migration. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-11-01 Lillian K Fritz-Laylin,Margaret A Titus
Many eukaryotic cells, including animal cells and unicellular amoebae, use dynamic-actin networks to crawl across solid surfaces. Recent discoveries of actin-dependent crawling in additional lineages have sparked interest in understanding how and when this type of motility evolved. Tracing the evolution of cell crawling requires understanding the molecular mechanisms underlying motility. Here we outline
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Cortical tension promotes Kibra degradation via Par-1. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-30 Sherzod A Tokamov,Stephan Buiter,Anne Ullyot,Gordana Scepanovic,Audrey Miller Williams,Rodrigo Fernandez-Gonzalez,Sally Horne-Badovinac,Richard G Fehon
The Hippo pathway is an evolutionarily conserved regulator of tissue growth. Multiple Hippo signaling components are regulated via proteolytic degradation. However, how these degradation mechanisms are themselves modulated remains unexplored. Kibra is a key upstream pathway activator that promotes its own ubiquitin-mediated degradation upon assembling a Hippo signaling complex. Here, we demonstrate
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The cell-end protein Tea4 spatially regulates hyphal branch initiation and appressorium remodeling in the blast fungus Magnaporthe oryzae. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-30 Audra Mae Rogers,Rachel Taylor,Martin John Egan
The differentiation of specialized infection cells, called appressoria, from polarized germ tubes of the blast fungus Magnaporthe oryzae, requires remarkable remodeling of cell polarity and architecture, yet our understanding of this process remains incomplete. Here we investigate the behavior and role of cell-end marker proteins in appressorium remodeling and hyphal branch emergence. We show that
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Differences in cell shape, motility, and growth reflect chromosomal number variations that can be visualized with live-cell ChReporters. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-30 Michael P Tobin,Charlotte R Pfeifer,Peter Kuangzheng Zhu,Brandon H Hayes,Mai Wang,Manasvita Vashisth,Yuntao Xia,Steven H Phan,Susanna A Belt,Jerome Irianto,Dennis E Discher
Chromosome numbers often change dynamically in tumors and cultured cells, which complicates therapy as well as understanding genotype-mechanotype relationships. Here we use a live-cell "ChReporter" method to identify cells with a single chromosomal loss in efforts to better understand differences in cell shape, motility, and growth. We focus on a standard cancer line and first show clonal populations
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Cbl and Cbl-b independently regulate EGFR through distinct receptor interaction modes. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-30 Itziar Pinilla-Macua,Alexander Sorkin
Highly homologous E3 ubiquitin ligases, Cbl and Cbl-b, mediate ubiquitination of EGF receptor (EGFR), leading to its endocytosis and lysosomal degradation. Cbl and Cbl-b, are thought to function in a redundant manner by binding directly to phosphorylated Y1045 (pY1045) of EGFR and indirectly via the Grb2 adaptor. Unexpectedly, we found that inducible expression of Cbl or Cbl-b mutants lacking the E3
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Multiple quality control mechanisms monitor yeast chitin synthase folding in the endoplasmic reticulum. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-11 Noelia Sanchez,Nagore de Leon,Rosario Valle,Jia Jun Fung,Anton Khmelinskii,Cesar Roncero
The chitin synthase Chs3 is a multipass membrane protein whose trafficking is tightly controlled. Accordingly, its exit from the endoplasmic reticulum (ER) depends on several complementary mechanisms that ensure its correct folding. Despite its potential failure on its exit, Chs3 is very stable in this compartment, which suggests its poor recognition by ER quality control mechanisms such as endoplasmic
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Mutation of the PEBP-like domain of the mitoribosomal MrpL35/mL38 protein results in production of nascent chains with impaired capacity to assemble into OXPHOS complexes. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-04 Jodie M Box,Jessica M Anderson,Rosemary A Stuart
Located in the central protuberance region of the mitoribosome and mitospecific mL38 proteins display homology to PEBP (Phosphatidylethanolamine Binding Protein) proteins, a diverse family of proteins reported to bind anionic substrates/ligands and implicated in cellular signaling and differentiation pathways. In this study, we have performed a mutational analysis of the yeast mitoribosomal protein
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Targeting APEX2 to the mRNA encoding fatty acid synthase β in yeast identifies interacting proteins that control its abundance in the cell cycle. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-10-04 Heidi M Blank,Wendell P Griffith,Michael Polymenis
Profiling the repertoire of proteins associated with a given mRNA during the cell cycle is unstudied. Furthermore, it is easier to ask and answer what mRNAs a specific protein might bind to than the other way around. Here, we implemented an RNA-centric proximity labeling technology at different points in the cell cycle in highly synchronous yeast cultures. To understand how the abundance of FAS1, encoding
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p97/VCP Promotes the Recycling of Endocytic Cargo. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-27 Mona Kawan,Maria Körner,Andreas Schlosser,Alexander Buchberger
The endocytic pathway is of central importance for eukaryotic cells, as it enables uptake of extracellular materials, membrane protein quality control and recycling, as well as modulation of receptor signaling. While the ATPase p97 (VCP, Cdc48) has been found to be involved in the fusion of early endosomes and endolysosomal degradation, its role in endocytic trafficking is still incompletely characterized
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Fungal transglutaminase domain-containing proteins are involved in hyphal protection at the septal pore against wounding. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-27 Md Abdulla Al Mamun,Jun-Ichi Maruyama
Transglutaminase (TG) is a ubiquitous enzyme that crosslinks substrates. In humans, TG participates in blood clotting and wound healing. However, the functions related to the cellular protection of microbial TG are unknown. In filamentous fungi, we previously identified SppB, which contains the transglutaminase core (TGc) domain and functions in hyphal protection at the septal pore upon wounding. Here
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Exploring the "misfolding problem" by systematic discovery and analysis of functional-but-degraded proteins. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-20 Matthew P Flagg,Breanna Lam,Darren K Lam,Tiffany M Le,Andy Kao,Yousif I Slaiwa,Randolph Y Hampton
In both health and disease, the ubiquitin-proteasome system (UPS) degrades point mutants that retain partial function but have decreased stability compared with their wild-type counterparts. This class of UPS substrate includes routine translational errors and numerous human disease alleles, such as the most common cause of cystic fibrosis, ΔF508-CFTR. Yet, there is no systematic way to discover novel
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CRISPR-mediated reversion of oncogenic KRAS mutation results in increased proliferation and reveals independent roles of Ras and mTORC2 in the migration of A549 lung cancer cells. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-20 Alyssa N Werner,Avani I Kumar,Pascale G Charest
Although the RAS oncogene has been extensively studied, new aspects concerning its role and regulation in normal biology and cancer continue to be discovered. Recently, others and we have shown that the mechanistic Target of Rapamycin Complex 2 (mTORC2) is a Ras effector in Dictyostelium and mammalian cells. mTORC2 plays evolutionarily conserved roles in cell survival and migration and has been linked
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The C-terminus of α-Synuclein Regulates its Dynamic Cellular Internalization by Neurexin 1β. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-20 Melissa Birol,Isabella Ioana Douzoglou Muñoz,Elizabeth Rhoades
The aggregation of the disordered neuronal protein, α-Synuclein (αS), is the primary pathological feature of Parkinson's disease. Current hypotheses favor cell-to-cell spread of αS species as underlying disease progression, driving interest in identifying the molecular species and cellular processes involved in cellular internalization of αS. Prior work from our lab identified the chemically specific
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EHD2 regulates plasma membrane integrity and downstream insulin receptor signaling events. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-13 Mathis Neuhaus,Claes Fryklund,Holly Taylor,Andrea Borreguero-Muñoz,Franziska Kopietz,Hamidreza Ardalani,Oksana Rogova,Laura Stirrat,Shaun K Bremner,Peter Spégel,Nia J Bryant,Gwyn W Gould,Karin G Stenkula
Adipocyte dysfunction is a crucial driver of insulin resistance and type 2 diabetes. We identified EH domain-containing protein 2 (EHD2) as one of the most highly upregulated genes at the early stage of adipose-tissue expansion. EHD2 is a dynamin-related ATPase influencing several cellular processes, including membrane recycling, caveolae dynamics, and lipid metabolism. Here, we investigated the role
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Nascent adhesions shorten the period of lamellipodium protrusion through the Brownian ratchet mechanism. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-06 Keith R Carney,Akib M Khan,Samantha Stam,Shiela C Samson,Nikhil Mittal,Sangyoon J Han,Tamara C Bidone,Michelle C Mendoza
Directional cell migration is driven by the conversion of oscillating edge motion into lasting periods of leading edge protrusion. Actin polymerization against the membrane and adhesions control edge motion, but the exact mechanisms that determine protrusion period remain elusive. We addressed this by developing a computational model in which polymerization of actin filaments against a deformable membrane
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SPAK-dependent cotransporter activity mediates capillary adhesion and pressure during glioblastoma migration in confined spaces. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-06 Sung Hoon Lee,Muhammad Sulaiman Yousafzai,Kyle Mohler,Vikrant Yadav,Sorosh Amiri,Joanna Szuszkiewicz,Andre Levchenko,Jesse Rinehart,Michael Murrell
The invasive potential of glioblastoma cells is attributed to large changes in pressure and volume, driven by diverse elements, including the cytoskeleton and ion cotransporters. However, how the cell actuates changes in pressure and volume in confinement, and how these changes contribute to invasive motion is unclear. Here, we inhibited SPAK activity, with known impacts on the cytoskeleton and cotransporter
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MARCKS Effector Domain, a reversible lipid ligand, illuminates late stages of membrane fusion. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-06 Amy Orr,William Wickner
Yeast vacuolar HOPS tethers membranes, catalyzes trans-SNARE assembly between R- and Q-SNAREs, and shepherds SNAREs past early inhibition by Sec17. After partial SNARE zippering, fusion is driven slowly by either completion of SNARE zippering or by Sec17/Sec18, but rapid fusion needs zippering and Sec17/Sec18. Using reconstituted-vacuolar fusion, we find that MARCKS Effector Domain (MED) peptide, a
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Depicting a cellular space occupied by condensates. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-09-01 Daniel Liu,Margot Riggi,Hyun O Lee,Simon L Currie,David S Goodsell,Janet H Iwasa,Ofer Rog
Condensates have emerged as a new way to understand how cells are organized, and have been invoked to play crucial roles in essentially all cellular processes. In this view, the cell is occupied by numerous assemblies, each composed of member proteins and nucleic acids that preferentially interact with each other. However, available visual representations of condensates fail to communicate the growing
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Coordinated expression of replication-dependent histone genes from multiple loci promotes histone homeostasis in Drosophila. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-30 Ashlesha Chaubal,Justin M Waldern,Colin Taylor,Alain Laederach,William F Marzluff,Robert J Duronio
Production of large amounts of histone proteins during S phase is critical for proper chromatin formation and genome integrity. This process is achieved in part by the presence of multiple copies of replication dependent (RD) histone genes that occur in one or more clusters in metazoan genomes. In addition, RD histone gene clusters are associated with a specialized nuclear body, the histone locus body
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Loss of EGF receptor polarity enables homeostatic imbalance in epithelial-cell models. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-30 Cathleen R Carlin,Syntyche Ngalula
The polarized distribution of membrane proteins into apical and basolateral domains provides the basis for specialized functions of epithelial tissues. The EGF receptor (EGFR) plays important roles in embryonic development, adult-epithelial tissue homeostasis, and growth and survival of many carcinomas. Typically targeted to basolateral domains, there is also considerable evidence of EGFR sorting plasticity
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The kinesin-5 tail and bipolar minifilament domains are the origin of its microtubule crosslinking and sliding activity. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-23 Stanley Nithianantham,Malina K Iwanski,Ignas Gaska,Himanshu Pandey,Tatyana Bodrug,Sayaka Inagaki,Jennifer Major,Gary J Brouhard,Larissa Gheber,Steven S Rosenfeld,Scott Forth,Adam G Hendricks,Jawdat Al-Bassam
Kinesin-5 crosslinks and slides apart microtubules to assemble, elongate, and maintain the mitotic spindle. Kinesin-5 is a tetramer, where two N-terminal motor domains are positioned at each end of the motor, and the coiled-coil stalk domains are organized into a tetrameric bundle through the bipolar assembly (BASS) domain. To dissect the function of the individual structural elements of the motor
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The SNARE-associated protein Sft2 functions in Imh1-mediated SNARE recycling transport upon ER stress. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-23 Chun-Chi Lai,Wan-Yun Chiu,Yan-Ting Chen,Chia-Lu Wu,Fang-Jen S Lee
Vesicular trafficking involving SNARE proteins play a crucial role in the delivery of cargo to the target membrane. Arf-like protein 1 (Arl1) is an important regulator of the endosomal trans-Golgi network (TGN) and secretory trafficking. In yeast, ER stress-enhances Arl1 activation and Golgin Imh1 recruitment to the late-Golgi. Although Arl1 and Imh1 are critical for GARP-mediated endosomal SNARE-recycling
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Temporal control of contact site formation reveals a relationship between mitochondrial division and Num1-mediated mitochondrial tethering. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-16 Clare S Harper,Jason C Casler,Laura L Lackner
Mitochondrial division is critical for maintenance of mitochondrial morphology and cellular homeostasis. Previous studies have suggested that the mitochondria-ER-cortex anchor (MECA), a tripartite membrane contact site between mitochondria, the ER, and the plasma membrane, is involved in mitochondrial division. However, its role is poorly understood. We developed a system to control MECA formation
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Hydrostatic Pressure Sensing by WNK kinases. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-16 John M Humphreys,Liliana R Teixeira,Radha Akella,Haixia He,Ashari R Kannangara,Kamil Sekulski,John Pleinis,Joanna Liwocha,Jenny Jiou,Kelly A Servage,Kim Orth,Lukasz Joachimiak,Josep Rizo,Melanie H Cobb,Chad A Brautigam,Aylin R Rodan,Elizabeth J Goldsmith
Previous study has demonstrated that the WNK kinases 1 and 3 are direct osmosensors consistent with their established role in cell-volume control. WNK kinases may also be regulated by hydrostatic pressure. Hydrostatic pressure applied to cells in culture with N2 gas or to Drosophila Malpighian tubules by centrifugation induces phosphorylation of downstream effectors of endogenous WNKs. In vitro, the
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Axonal transport of Frizzled5 by Alcadein α-containing vesicles is associated with kinesin-1. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-16 Yuzuha Shiraki,Monet Mitsuma,Ritsuko Takada,Saori Hata,Akira Kitamura,Shinji Takada,Masataka Kinjo,Hidenori Taru,Ulrike C Müller,Tohru Yamamoto,Yuriko Sobu,Toshiharu Suzuki
Alcadein α (Alcα) and amyloid-β protein precursor (APP) are cargo receptors that associate vesicles with kinesin-1. These vesicles, which contain either Alcα or APP, transport various proteins/cargo molecules into axon nerve terminals. Here, we analyzed immune-isolated Alcα- and APP-containing vesicles of adult mouse brains with LC-MS/MS and identified proteins present in vesicles that contained either
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A dedicated cytoplasmic container collects extrachromosomal DNA away from the mammalian nucleus. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-09 Laura Schenkel,Xuan Wang,Nhung Le,Michael Burger,Ruth Kroschewski
Expression from transfected plasmid DNA is generally transient, but it is unclear what process terminates it. We show that DNA entering mammalian cells is rapidly surrounded by a double membrane in the cytoplasm, in some cases after leaving the nucleus. This cytoplasmic container, termed exclusome, frequently also contains extrachromosomal telomeric DNA, and is maintained by the cell over several division
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Osh-dependent and -independent Regulation of PI4P Levels During Polarized Growth of Saccharomyces cerevisiae. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-09 Lindsay A Heckle,Keith G Kozminski
Polarized secretion facilitates polarized cell growth. For a secretory vesicle to dock at the plasma membrane, it must mature with a progressive association or dissociation of molecules that are, respectively, necessary for or inhibitory to vesicle docking, including an exchange of Rab GTPases. In current models, oxysterol-binding protein homologue 4 (Osh4p) establishes a phosphatidylinositol 4-phosphate
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Endoplasmic Reticulum Exit Sites scale with somato-dendritic size in neurons. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-09 Ruben Land,Richard Fetter,Xing Liang,Christopher P Tzeng,Caitlin A Taylor,Kang Shen
Nervous systems exhibit dramatic diversity in cell morphology and size. How neurons regulate their biosynthetic and secretory machinery to support such diversity is not well understood. Endoplasmic reticulum exit sites (ERESs) are essential for maintaining secretory flux, and are required for normal dendrite development, but how neurons of different size regulate secretory capacity remains unknown
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Results from the MBoC Preprint Highlight experiment. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-01 Michael M Lacy,Matthew D Welch
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Noncanonical binding of transcription factors: time to revisit specificity? Mol. Biol. Cell (IF 3.3) Pub Date : 2023-08-01 Md Abul Hassan Samee
Transcription factors (TFs) are one of the most studied classes of DNA-binding proteins that have a direct functional impact on gene transcription and thus, on human physiology and disease. The mechanisms that TFs use for recognizing target DNA binding sites have been studied for nearly five decades, yet they remain poorly understood. It is classically assumed that a TF recognizes a specific sequence
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Meiosis II spindle disassembly requires two distinct pathways. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-07-12 Brian C Seitz,Xheni Mucelli,Maira Majano,Zoey Wallis,Ashley C Dodge,Catherine Carmona,Matthew Durant,Sharra Maynard,Linda S Huang
During exit from meiosis II, cells undergo several structural rearrangements, including disassembly of the meiosis II spindles and cytokinesis. Each of these changes is regulated to ensure that they occur at the proper time. Previous studies have demonstrated that both SPS1, which encodes a STE20-family GCKIII kinase, and AMA1, which encodes a meiosis-specific activator of the Anaphase Promoting Complex
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Misregulation of cell cycle-dependent methylation of budding yeast CENP-A contributes to chromosomal instability. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-07-12 Prashant K Mishra,Wei-Chun Au,Pedro G Castineira,Nazrin Ali,John Stanton,Lars Boeckmann,Yoshimitsu Takahashi,Michael Costanzo,Charles Boone,Kerry S Bloom,Peter H Thorpe,Munira A Basrai
Centromere (CEN) identity is specified epigenetically by specialized nucleosomes containing evolutionarily conserved CEN-specific histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae, CENP-A in humans), which is essential for faithful chromosome segregation. However, the epigenetic mechanisms that regulate Cse4 function have not been fully defined. In this study, we show that cell cycle-dependent
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Evidence that tissue recoil in the early Drosophila embryo is a passive not active process. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-07-05 Amanda Nicole Goldner,Salena M Fessehaye,Nataly Rodriguez,Kelly Ann Mapes,Miriam Osterfield,Konstantin Doubrovinski
Understanding tissue morphogenesis is impossible without knowing the mechanical properties of the tissue being shaped. Although techniques for measuring tissue material properties are continually being developed, methods for determining how individual proteins contribute to mechanical properties are very limited. Here, we developed two complementary techniques for the acute inactivation of spaghetti
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A new layer of regulation of chromosomal passenger complex (CPC) translocation in budding yeast. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-07-05 Delaney Sherwin,Emily Gutierrez-Morton,Michael Bokros,Cory Haluska,Yanchang Wang
The conserved chromosomal passenger complex (CPC) consists of Ipl1Aurora-B, Sli15INCENP, Bir1Survivin, and Nbl1Borealin, and localizes at the kinetochore/centromere to correct kinetochore attachment errors and to prevent checkpoint silencing. After anaphase entry, the CPC moves from the kinetochore/centromere to the spindle. In budding yeast, CPC subunit Sli15 is phosphorylated by both cyclin-dependent
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Matrix obstructions cause multiscale disruption in collective epithelial migration by suppressing leader cell function. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-28 Ye Lim Lee,Jairaj Mathur,Christopher Walter,Hannah Zmuda,Amit Pathak
During disease and development, physical changes in extracellular matrix cause jamming, unjamming, and scattering in epithelial migration. However, whether disruptions in matrix topology alter collective cell migration speed and cell-cell coordination remains unclear. We microfabricated substrates with stumps of defined geometry, density, and orientation, which create obstructions for migrating epithelial
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A conserved STRIPAK complex is required for autophagy in muscle tissue. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-28 Yungui Guo,Qiling Zeng,David Brooks,Erika R Geisbrecht
Autophagy is important for cellular homeostasis and to prevent the abnormal accumulation of proteins. While many proteins that comprise the canonical autophagy pathway have been characterized, the identification of new regulators may help understand tissue and/or stress-specific responses. Using an in-silico approach, we identified Striatin interacting protein (Strip), MOB kinase activator 4, and fibroblast
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Scaling of nuclear numbers and their spatial arrangement in skeletal muscle cell size regulation. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-07-01 Kenth-Arne Hansson,Einar Eftestøl
Many cells display considerable functional plasticity and depend on the regulation of numerous organelles and macromolecules for their maintenance. In large cells, organelles also need to be carefully distributed to supply the cell with essential resources and regulate intracellular activities. Having multiple copies of the largest eukaryotic organelle, the nucleus, epitomizes the importance of scaling
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The E3 ligase Poe promotes Pericentrin degradation. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-21 Brian J Galletta,Ramya Varadarajan,Carey J Fagerstrom,Bing Yang,Karen Plevock Haase,Katherine McJunkin,Nasser M Rusan
Centrosomes are essential parts of diverse cellular processes, and precise regulation of the levels of their constituent proteins is critical for their function. One such protein is Pericentrin (PCNT) in humans and Pericentrin-like protein (PLP) in Drosophila. Increased PCNT expression and its protein accumulation are linked to clinical conditions including cancer, mental disorders, and ciliopathies
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Serotonin 5-HT7 receptor slows down the Gs protein: a single molecule perspective. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-21 Aleš Petelák,Nevin A Lambert,Alexey Bondar
The 5-hydroxytryptamine (serotonin) receptor type 7 (5-HT7R) is a G protein-coupled receptor present primarily in the nervous system and gastrointestinal tract, where it regulates mood, cognition, digestion, and vasoconstriction. 5-HT7R has previously been shown to bind to its cognate stimulatory Gs protein in the inactive state. This phenomenon, termed "inverse coupling," is thought to counteract
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A fine balance among key biophysical factors is required for recovery of bipolar mitotic spindle from monopolar and multipolar abnormalities. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-21 Xiaochu Li,Mathew Bloomfield,Alexandra Bridgeland,Daniela Cimini,Jing Chen
During mitosis, equal partitioning of chromosomes into two daughter cells requires assembly of a bipolar mitotic spindle. Because the spindle poles are each organized by a centrosome in animal cells, centrosome defects can lead to monopolar or multipolar spindles. However, the cell can effectively recover the bipolar spindle by separating the centrosomes in monopolar spindles and clustering them in
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Cell contractility drives mechanical memory of oral squamous cell carcinoma. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-21 So Youn Moon,Paloma Santos de Campos,Bibiana Franzen Matte,Jesse K Placone,Virgı Lio G Zanella,Manoela D Martins,Marcelo Lazzaron Lamers,Adam J Engler
Matrix stiffening is ubiquitous in solid tumors and can direct epithelial-mesenchymal transition (EMT) and cancer cell migration. Stiffened niche can even cause poorly invasive oral squamous cell carcinoma (OSCC) cell lines to acquire a less adherent, more migratory phenotype, but mechanisms and durability of this acquired "mechanical memory" are unclear. Here, we observed that contractility and its
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Efficient fusion requires a membrane anchor on the vacuolar Qa-SNARE. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-14 William Wickner,Karina Lopes,Hongki Song,Josep Rizo,Amy Orr
As a prelude to fusion, the R-SNARE on one membrane zippers with Qa-, Qb-, and Qc-SNAREs from its apposed fusion partner, forming a four-helical bundle that draws the two membranes together. Because Qa- and Qb-SNAREs are anchored to the same membrane and are adjacent in the 4-SNARE bundle, their two anchors might be redundant. Using the recombinant pure protein catalysts of yeast vacuole fusion, we
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Interaction of the sorting nexin 25 homologue Snazarus with Rab11 balances endocytic and secretory transport and maintains the ultrafiltration diaphragm in nephrocytes. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-14 Tamás Maruzs,Dalma Feil-Börcsök,Enikő Lakatos,Gábor Juhász,András Blastyák,Dávid Hargitai,Steve Jean,Péter Lőrincz,Gábor Juhász
Proper balance of exocytosis and endocytosis is important for the maintenance of plasma membrane lipid and protein homeostasis. This is especially critical in human podocytes and the podocyte-like Drosophila nephrocytes that both use a delicate diaphragm system with evolutionarily conserved components for ultrafiltration. Here, we show that the sorting nexin 25 homologue Snazarus (Snz) binds to Rab11
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Role of 2-hydroxy acyl-CoA lyase HACL2 in odd-chain fatty acid production via α-oxidation in vivo. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-07 Keisuke Mori,Tatsuro Naganuma,Akio Kihara
Although most fatty acids (FAs) are even chain, certain tissues, including brain, contain relatively large quantities of odd-chain FAs in their sphingolipids. One of the pathways producing odd-chain FAs is the α-oxidation of 2-hydroxy (2-OH) FAs, where 2-OH acyl-CoA lyases (HACL1 and HACL2) catalyze the key cleavage reaction. However, the contribution of each HACL to odd-chain FA production in vivo
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Enabled primarily controls filopodial morphology, not actin organization, in the TSM1 growth cone in Drosophila. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-24 Hsiao Yu Fang,Rameen Forghani,Akanni Clarke,Philip G McQueen,Aravind Chandrasekaran,Kate M O'Neill,Wolfgang Losert,Garegin A Papoian,Edward Giniger
Ena/VASP proteins are processive actin polymerases that are required throughout animal phylogeny for many morphogenetic processes, including axon growth and guidance. Here we use in vivo live imaging of morphology and actin distribution to determine the role of Ena in promoting the growth of the TSM1 axon of the Drosophila wing. Altering Ena activity causes stalling and misrouting of TSM1. Our data
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Divergent regulation of α-arrestin ARRDC3 function by ubiquitination. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-24 Helen Wedegaertner,Oye Bosompra,Irina Kufareva,JoAnn Trejo
The α-arrestin ARRDC3 is a recently discovered tumor suppressor in invasive breast cancer that functions as a multifaceted adaptor protein to control protein trafficking and cellular signaling. However, the molecular mechanisms that control ARRDC3 function are unknown. Other arrestins are known to be regulated by posttranslational modifications, suggesting that ARRDC3 may be subject to similar regulatory
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Challenges and opportunities in maintaining research momentum at a primarily undergraduate institution. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-06-01 Mariana Torrente,Ozlem Dilek
Conferences and meetings hosted by scientific societies usually include sessions on how to navigate the academic faculty job search and the initial setup of a laboratory, or how to identify and pursue early-career grant funding opportunities. However, there is not much professional development support available beyond this stage. Faculty may have set up the research lab and have recruited students
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High extracellular glucose promotes cell motility by modulating cell deformability and contractility via the cAMP-RhoA-ROCK axis in human breast cancer cells. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-17 Mijung Oh,Skylar Batty,Nayan Banerjee,Tae-Hyung Kim
The mechanical properties, or mechanotypes, of cells are largely determined by their deformability and contractility. The ability of cancer cells to deform and generate contractile force is critical in multiple steps of metastasis. Identifying soluble cues that regulate cancer cell mechanotypes and understanding the underlying molecular mechanisms regulating these cellular mechanotypes could provide
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The short-chain fatty acid acetate coordinates with CD30 to modulate T-cell survival. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-10 Junfang Lyu,Ziyi Li,Jessica P Roberts,Yue A Qi,Jianhua Xiong
As an important substrate for cell metabolism, the short-chain fatty acid acetate emerges as a regulator of cell fate and function. However, its role in T-cell survival and its underlying mechanisms remain largely unknown. Here, we demonstrate that acetate modulates T-cell apoptosis via potentiation of α-tubulin acetylation. We further show that acetate treatment effectively increases the expression
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The Tetrahymena bcd1 mutant implicates endosome trafficking in ciliate, cortical pattern formation. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-10 Eric S Cole,Wolfgang Maier,Ewa Joachimiak,Yu-Yang Jiang,Chinkyu Lee,Erik Collet,Carl Chmelik,Daniel P Romero,Douglas Chalker,Nurudeen K Alli,Tina M Ruedlin,Courtney Ozzello,Jacek Gaertig
Ciliates, such as Tetrahymena thermophila, evolved complex mechanisms to determine both the location and dimensions of cortical organelles such as the oral apparatus (OA: involved in phagocytosis), cytoproct (Cyp: for eliminating wastes), and contractile vacuole pores (CVPs: involved in water expulsion). Mutations have been recovered in Tetrahymena that affect both the localization of such organelles
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Polo-like kinase 4 homodimerization and condensate formation regulate its own protein levels but are not required for centriole assembly. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-10 John M Ryniawec,Daniel W Buster,Lauren K Slevin,Cody J Boese,Anastasia Amoiroglou,Spencer M Dean,Kevin C Slep,Gregory C Rogers
Polo-like kinase 4 (Plk4) is the master-regulator of centriole assembly, and cell cycle-dependent regulation of its activity maintains proper centrosome number. During most of the cell cycle, Plk4 levels are nearly undetectable due to its ability to autophosphorylate and trigger its own ubiquitin-mediated degradation. However, during mitotic exit, Plk4 forms a single aggregate on the centriole surface
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Calcium-binding Cab45 regulates the polarized apical secretion of soluble proteins in epithelial cells. Mol. Biol. Cell (IF 3.3) Pub Date : 2023-05-10 Dandan Liu,Simona Paladino,Chiara Zurzolo,Stéphanie Lebreton
Protein secretion is essential for epithelial tissue homoeostasis and therefore has to be tightly regulated. However, while the mechanisms regulating polarized protein sorting and trafficking have been widely studied in the past decade, those governing polarized secretion remain elusive. The calcium manganese pump SPCA1 and the calcium-binding protein Cab45 were recently shown to regulate the secretion