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A guide to membrane atg8ylation and autophagy with reflections on immunity. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-14 Vojo Deretic,Michael Lazarou
The process of membrane atg8ylation, defined herein as the conjugation of the ATG8 family of ubiquitin-like proteins to membrane lipids, is beginning to be appreciated in its broader manifestations, mechanisms, and functions. Classically, membrane atg8ylation with LC3B, one of six mammalian ATG8 family proteins, has been viewed as the hallmark of canonical autophagy, entailing the formation of characteristic
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A mitochondrial contribution to anti-inflammatory shear stress signaling in vascular endothelial cells. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-13 Brian G Coon,Sushma Timalsina,Matteo Astone,Zhen W Zhuang,Jennifer Fang,Jinah Han,Jurgen Themen,Minhwan Chung,Young Joo Yang-Klingler,Mukesh Jain,Karen K Hirschi,Ai Yamamato,Louis-Eric Trudeau,Massimo Santoro,Martin A Schwartz
Atherosclerosis, the major cause of myocardial infarction and stroke, results from converging inflammatory, metabolic, and biomechanical factors. Arterial lesions form at sites of low and disturbed blood flow but are suppressed by high laminar shear stress (LSS) mainly via transcriptional induction of the anti-inflammatory transcription factor, Kruppel-like factor 2 (Klf2). We therefore performed a
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Ubiquitinating the way to T cell metabolism. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-13 Sarah McPhedran,Julian J Lum
In this issue, Harris et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202203095) show that phosphofructokinase is a substrate for ubiquitination by Fbxo7, a key protein in the ubiquitination pathway. Their findings point to a new interplay between metabolic enzyme degradation in the regulation of T cells.
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A close shave: How SARS-CoV-2 induces the loss of cilia. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-13 Barbara F Fonseca,Lisa A Chakrabarti
Wang et al. report in this issue (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108015) that the SARS-CoV-2 protein ORF10 increases the activity of the E3 ligase CUL2ZYG11B, leading to the degradation of multiple ciliary proteins. The resulting loss of cilia may facilitate the spread of SARS-CoV-2 in the respiratory tree.
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PEAK1 Y635 phosphorylation regulates cell migration through association with Tensin3 and integrins. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-10 Alba Zuidema,Paul Atherton,Maaike Kreft,Liesbeth Hoekman,Onno B Bleijerveld,Nagarjuna Nagaraj,Nanpeng Chen,Reinhard Fässler,Arnoud Sonnenberg
Integrins mediate cell adhesion by connecting the extracellular matrix to the intracellular cytoskeleton and orchestrate signal transduction in response to chemical and mechanical stimuli by interacting with many cytoplasmic proteins. We used BioID to interrogate the interactomes of β1 and β3 integrins in epithelial cells and identified PEAK1 as an interactor of the RGD-binding integrins α5β1, αVβ3
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SARS-CoV-2 ORF10 impairs cilia by enhancing CUL2ZYG11B activity. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-08 Liying Wang,Chao Liu,Bo Yang,Haotian Zhang,Jian Jiao,Ruidan Zhang,Shujun Liu,Sai Xiao,Yinghong Chen,Bo Liu,Yanjie Ma,Xuefeng Duan,Yueshuai Guo,Mengmeng Guo,Bingbing Wu,Xiangdong Wang,Xingxu Huang,Haitao Yang,Yaoting Gui,Min Fang,Luo Zhang,Shuguang Duo,Xuejiang Guo,Wei Li
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal pathogen of the ongoing global pandemic of coronavirus disease 2019 (COVID-19). Loss of smell and taste are symptoms of COVID-19, and may be related to cilia dysfunction. Here, we found that the SARS-CoV-2 ORF10 increases the overall E3 ligase activity of the CUL2ZYG11B complex by interacting with ZYG11B. Enhanced CUL2ZYG11B
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Coro1B and Coro1C regulate lamellipodia dynamics and cell motility by tuning branched actin turnover. J. Cell Biol. (IF 10.539) Pub Date : 2022-06-03 Zayna T King,Mitchell T Butler,Max A Hockenberry,Bhagawat C Subramanian,Priscila F Siesser,David M Graham,Wesley R Legant,James E Bear
Actin filament dynamics must be precisely controlled in cells to execute behaviors such as vesicular trafficking, cytokinesis, and migration. Coronins are conserved actin-binding proteins that regulate several actin-dependent subcellular processes. Here, we describe a new conditional knockout cell line for two ubiquitous coronins, Coro1B and Coro1C. These coronins, which strongly co-localize with Arp2/3-branched
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Sheldon Penman: Visionary of cell form and function. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-31 Thoru Pederson
Sheldon Penman made major contributions to the field of RNA synthesis and, more broadly, the nexus between cellular form and gene readout. He will be remembered for his creativity and breadth of expertise, as well as his opposition to what he believed were threatening incursions into science by corporate interests.
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Border cell polarity and collective migration require the spliceosome component Cactin. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-25 Guangxia Miao,Li Guo,Denise J Montell
Border cells are an in vivo model for collective cell migration. Here, we identify the gene cactin as essential for border cell cluster organization, delamination, and migration. In Cactin-depleted cells, the apical proteins aPKC and Crumbs (Crb) become abnormally concentrated, and overall cluster polarity is lost. Apically tethering excess aPKC is sufficient to cause delamination defects, and relocalizing
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Sara Wickström: The forces controlling our cell fate. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-24 Lucia Morgado-Palacin
Sara Wickström combines biophysics, next-generation sequencing, and basic cell biology to investigate how cellular forces regulate the fate and position of stem cells within epithelial tissues.
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SMGL-1/NBAS acts as a RAB-8 GEF to regulate unconventional protein secretion. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-23 Xianghong Wang,Xinxin Li,Junkai Wang,Jiabin Wang,Can Hu,Jia Zeng,Anbing Shi,Long Lin
Unconventional protein secretion (UPS) pathways are conserved across species. However, the underlying mechanisms that regulate Golgi-bypassing UPS of integral proteins remain elusive. In this study, we show that RAB-8 and SMGL-1/NBAS are required for the UPS of integral proteins in C. elegans intestine. SMGL-1 resides in the ER-Golgi intermediate compartment and adjacent RAB-8-positive structures,
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Reconstitution and mechanistic dissection of the human microtubule branching machinery. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-23 Yaqian Zhang,Xing Hong,Shasha Hua,Kai Jiang
Branching microtubule (MT) nucleation is mediated by the augmin complex and γ-tubulin ring complex (γ-TuRC). However, how these two complexes work together to promote this process remains elusive. Here, using purified components from native and recombinant sources, we demonstrate that human augmin and γ-TuRC are sufficient to reconstitute the minimal MT branching machinery, in which NEDD1 bridges between
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Regulated targeting of the monotopic hairpin membrane protein Erg1 requires the GET pathway. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-19 Ákos Farkas,Henning Urlaub,Katherine E Bohnsack,Blanche Schwappach
The guided entry of tail-anchored proteins (GET) pathway targets C-terminally anchored transmembrane proteins and protects cells from lipotoxicity. Here, we reveal perturbed ergosterol production in ∆get3 cells and demonstrate the sensitivity of GET pathway mutants to the sterol synthesis inhibiting drug terbinafine. Our data uncover a key enzyme of sterol synthesis, the hairpin membrane protein squalene
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Transcytosis and trans-synaptic retention by postsynaptic ErbB4 underlie axonal accumulation of NRG3. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-17 Tanveer Ahmad,Detlef Vullhorst,Rituparna Chaudhuri,Carlos M Guardia,Nisha Chaudhary,Irina Karavanova,Juan S Bonifacino,Andres Buonanno
Neuregulins (NRGs) are EGF-like ligands associated with cognitive disorders. Unprocessed proNRG3 is cleaved by BACE1 to generate the mature membrane-bound NRG3 ligand, but the subcellular site of proNRG3 cleavage, mechanisms underlying its transport into axons, and presynaptic accumulation remain unknown. Using an optogenetic proNRG3 cleavage reporter (LA143-NRG3), we investigate the spatial-temporal
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DPYSL2 interacts with JAK1 to mediate breast cancer cell migration. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-16 Areej Abu Rmaileh,Balakrishnan Solaimuthu,Anees Khatib,Shirel Lavi,Mayur Tanna,Arata Hayashi,Michal Ben Yosef,Michal Lichtenstein,Nir Pillar,Yoav D Shaul
The intricate neuronal wiring during development requires cytoskeletal reorganization orchestrated by signaling cues. Because cytoskeletal remodeling is a hallmark of cell migration, we investigated whether metastatic cancer cells exploit axon guidance proteins to migrate. Indeed, in breast cancer patients, we found a significant correlation between mesenchymal markers and the expression of dihydropyrimidinase-like
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Filamin FLN-2 promotes MVB biogenesis by mediating vesicle docking on the actin cytoskeleton. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-16 Leiling Shi,Youli Jian,Meijiao Li,Tianchao Hao,Chonglin Yang,Xiaochen Wang
Multivesicular bodies (MVBs) contain intralumenal vesicles that are delivered to lysosomes for degradation or released extracellularly for intercellular signaling. Here, we identified Caenorhabditis elegans filamin FLN-2 as a novel regulator of MVB biogenesis. FLN-2 co-localizes with V-ATPase subunits on MVBs, and the loss of FLN-2 affects MVB biogenesis, reducing the number of MVBs in C. elegans hypodermis
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Killing cells using light (activated) sabers. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-16 Stephen W G Tait
Many types of regulated cell death exist, however the non-cell autonomous effects of specific forms of cell death remain poorly understood. Addressing this, Shkarina et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202109038) describe an optogenetic method to activate distinct modes of cell death in select cells.
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Paradoxical roles of caspase-3 in regulating cell survival, proliferation, and tumorigenesis. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-12 Ebrahim Eskandari,Connie J Eaves
Caspase-3 is a widely expressed member of a conserved family of proteins, generally recognized for their activated proteolytic roles in the execution of apoptosis in cells responding to specific extrinsic or intrinsic inducers of this mode of cell death. However, accumulating evidence indicates that caspase-3 also plays key roles in regulating the growth and homeostatic maintenance of both normal and
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New insights into IRE1α activation and function in anti-tumor immunity. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-11 Susan E Logue,Adrienne M Gorman,Afshin Samali
Logue, Gorman, and Samali highlight a study by Guttman and colleagues (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202111068) that shows exogenous antigen peptides imported into the ER can activate the ER stress sensor IRE1α, attenuating cross-presentation by dendritic cells.
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VMP1 and TMEM41B are essential for DMV formation during β-coronavirus infection. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-10 Mingming Ji,Meng Li,Long Sun,Hongyu Zhao,Ying Li,Lulu Zhou,Zhenni Yang,Xin Zhao,Wenyan Qu,Hanbing Xue,Ze Zheng,Yiming Li,Hongyu Deng,Yan G Zhao
β-coronaviruses reshape host cell endomembranes to form double-membrane vesicles (DMVs) for genome replication and transcription. Ectopically expressed viral nonstructural proteins nsp3 and nsp4 interact to zipper and bend the ER for DMV biogenesis. Genome-wide screens revealed the autophagy proteins VMP1 and TMEM41B as important host factors for SARS-CoV-2 infection. Here, we demonstrated that DMV
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Too close for comfort? Endomembranes promote missegregation by enclosing lost chromosomes. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-10 Lisa Donker,Susana A Godinho
Correct segregation of chromosomes during mitosis is essential to prevent aneuploidy. In this issue, Ferrandiz et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202203021) show that endomembranes can promote chromosome missegregation by "ensheathing" misaligned chromosomes, preventing their integration into the metaphase plate. Their findings point toward endomembranes as a potential risk factor
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Induced nanoscale membrane curvature bypasses the essential endocytic function of clathrin. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-09 Robert C Cail,Cyna R Shirazinejad,David G Drubin
During clathrin-mediated endocytosis (CME), flat plasma membrane is remodeled to produce nanometer-scale vesicles. The mechanisms underlying this remodeling are not completely understood. The ability of clathrin to bind membranes of distinct geometries casts uncertainty on its specific role in curvature generation/stabilization. Here, we used nanopatterning to produce substrates for live-cell imaging
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Cell cortex regulation by the planar cell polarity protein Prickle1. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-05 Yunyun Huang,Rudolf Winklbauer
The planar cell polarity pathway regulates cell polarity, adhesion, and rearrangement. Its cytoplasmic core components Prickle (Pk) and Dishevelled (Dvl) often localize as dense puncta at cell membranes to form antagonizing complexes and establish cell asymmetry. In vertebrates, Pk and Dvl have been implicated in actomyosin cortex regulation, but the mechanism of how these proteins control cell mechanics
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STING controls energy stress-induced autophagy and energy metabolism via STX17. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-05 Yueguang Rong,Shen Zhang,Nilay Nandi,Zhe Wu,Linsen Li,Yang Liu,Yuehan Wei,Yuan Zhao,Weigang Yuan,Chuchu Zhou,Guanghua Xiao,Beth Levine,Nan Yan,Shan Mou,Liufu Deng,Zaiming Tang,Xiaoxia Liu,Helmut Kramer,Qing Zhong
The stimulator of interferon genes (STING) plays a critical role in innate immunity. Emerging evidence suggests that STING is important for DNA or cGAMP-induced non-canonical autophagy, which is independent of a large part of canonical autophagy machineries. Here, we report that, in the absence of STING, energy stress-induced autophagy is upregulated rather than downregulated. Depletion of STING in
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SHIP164 is a chorein motif lipid transfer protein that controls endosome-Golgi membrane traffic. J. Cell Biol. (IF 10.539) Pub Date : 2022-05-02 Michael G Hanna,Patreece H Suen,Yumei Wu,Karin M Reinisch,Pietro De Camilli
Cellular membranes differ in protein and lipid composition as well as in the protein-lipid ratio. Thus, progression of membranous organelles along traffic routes requires mechanisms to control bilayer lipid chemistry and their abundance relative to proteins. The recent structural and functional characterization of VPS13-family proteins has suggested a mechanism through which lipids can be transferred
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Endomembranes promote chromosome missegregation by ensheathing misaligned chromosomes J. Cell Biol. (IF 10.539) Pub Date : 2022-04-29 Nuria Ferrandiz,Laura Downie,Georgina P. Starling,Stephen J. Royle
Errors in mitosis that cause chromosome missegregation lead to aneuploidy and micronucleus formation, which are associated with cancer. Accurate segregation requires the alignment of all chromosomes by the mitotic spindle at the metaphase plate, and any misalignment must be corrected before anaphase is triggered. The spindle is situated in a membrane-free “exclusion zone”; beyond this zone, endomembranes
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Interphase microtubule disassembly is a signaling cue that drives cell rounding at mitotic entry J. Cell Biol. (IF 10.539) Pub Date : 2022-04-28 Kévin Leguay,Barbara Decelle,Islam E. Elkholi,Michel Bouvier,Jean-François Côté,Sébastien Carréno
At mitotic entry, reorganization of the actomyosin cortex prompts cells to round-up. Proteins of the ezrin, radixin, and moesin family (ERM) play essential roles in this process by linking actomyosin forces to the plasma membrane. Yet, the cell-cycle signal that activates ERMs at mitotic entry is unknown. By screening a compound library using newly developed biosensors, we discovered that drugs that
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Lineage tracing clarifies the cellular origin of tissue-resident macrophages in the developing heart. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-28 Kuo Liu,Hengwei Jin,Muxue Tang,Shaohua Zhang,Xueying Tian,Mingjun Zhang,Ximeng Han,Xiuxiu Liu,Juan Tang,Wenjuan Pu,Yan Li,Lingjuan He,Zhongzhou Yang,Kathy O Lui,Bin Zhou
Tissue-resident macrophages play essential functions in the maintenance of tissue homeostasis and repair. Recently, the endocardium has been reported as a de novo hemogenic site for the contribution of hematopoietic cells, including cardiac macrophages, during embryogenesis. These observations challenge the current consensus that hematopoiesis originates from the hemogenic endothelium within the yolk
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Visualizing intra-Golgi localization and transport by side-averaging Golgi ministacks. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-25 Hieng Chiong Tie,Divyanshu Mahajan,Lei Lu
The mammalian Golgi comprises tightly adjacent and flattened membrane sacs called cisternae. We still do not understand the molecular organization of the Golgi and intra-Golgi transport of cargos. One of the most significant challenges to studying the Golgi is resolving Golgi proteins at the cisternal level under light microscopy. We have developed a side-averaging approach to visualize the cisternal
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Tumor suppressor BAP1 nuclear import is governed by transportin-1. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-21 Tzu-Jing Yang,Tian-Neng Li,Rih-Sheng Huang,Max Yu-Chen Pan,Shu-Yu Lin,Steven Lin,Kuen-Phon Wu,Lily Hui-Ching Wang,Shang-Te Danny Hsu
Subcellular localization of the deubiquitinating enzyme BAP1 is deterministic for its tumor suppressor activity. While the monoubiquitination of BAP1 by an atypical E2/E3-conjugated enzyme UBE2O and BAP1 auto-deubiquitination are known to regulate its nuclear localization, the molecular mechanism by which BAP1 is imported into the nucleus has remained elusive. Here, we demonstrated that transportin-1
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Antigen-derived peptides engage the ER stress sensor IRE1α to curb dendritic cell cross-presentation. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-21 Ofer Guttman,Adrien Le Thomas,Scot Marsters,David A Lawrence,Lauren Gutgesell,Iratxe Zuazo-Gaztelu,Jonathan M Harnoss,Simone M Haag,Aditya Murthy,Geraldine Strasser,Zora Modrusan,Thomas Wu,Ira Mellman,Avi Ashkenazi
Dendritic cells (DCs) promote adaptive immunity by cross-presenting antigen-based epitopes to CD8+ T cells. DCs process internalized protein antigens into peptides that enter the endoplasmic reticulum (ER), bind to major histocompatibility type I (MHC-I) protein complexes, and are transported to the cell surface for cross-presentation. DCs can exhibit activation of the ER stress sensor IRE1α without
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Secretory autophagy maintains proteostasis upon lysosome inhibition. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-21 Tina A Solvik,Tan A Nguyen,Yu-Hsiu Tony Lin,Timothy Marsh,Eric J Huang,Arun P Wiita,Jayanta Debnath,Andrew M Leidal
The endolysosome system plays central roles in both autophagic degradation and secretory pathways, including the release of extracellular vesicles and particles (EVPs). Although previous work reveals important interconnections between autophagy and EVP-mediated secretion, our understanding of these secretory events during endolysosome inhibition remains incomplete. Here, we delineate a secretory autophagy
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Lena Ho: Micropeptides under the spotlight. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-20 Lucia Morgado-Palacin
Lena Ho studies small ORF-encoded peptides (SEPs; also known as micropeptides), with a particular focus on mitochondrial SEPs, and their role in vascular biology and immunometabolism.
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Actomyosin fibers DApPLE epithelial apical junctions. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-20 Alejandra R Manzano,Fernando Martín-Belmonte
Epithelial cell morphology is essential for cellular homeostasis, but the mechanisms by which cell shape is established remain unclear. In this study, Marivin et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202111002) identify DAPLE as a linker between polarity complexes and the actomyosin network at apical junctions. By recruiting CD2P and activating Gαβγ-mediated RhoA signaling, DAPLE ensures
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GET pathway mediates transfer of mislocalized tail-anchored proteins from mitochondria to the ER. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-20 Shunsuke Matsumoto,Suzuka Ono,Saori Shinoda,Chika Kakuta,Satoshi Okada,Takashi Ito,Tomoyuki Numata,Toshiya Endo
Tail-anchored (TA) membrane proteins have a potential risk to be mistargeted to the mitochondrial outer membrane (OM). Such mislocalized TA proteins can be extracted by the mitochondrial AAA-ATPase Msp1 from the OM and transferred to the ER for ER protein quality control involving ubiquitination by the ER-resident Doa10 complex. Yet it remains unclear how the extracted TA proteins can move to the ER
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SNX5 targets a monoamine transporter to the TGN for assembly into dense core vesicles by AP-3. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-15 Hongfei Xu,Fei Chang,Shweta Jain,Bradley Austin Heller,Xu Han,Yongjian Liu,Robert H Edwards
The time course of signaling by peptide hormones, neural peptides, and other neuromodulators depends on their storage inside dense core vesicles (DCVs). Adaptor protein 3 (AP-3) assembles the membrane proteins that confer regulated release of DCVs and is thought to promote their trafficking from endosomes directly to maturing DCVs. We now find that regulated monoamine release from DCVs requires sorting
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Optogenetic activators of apoptosis, necroptosis, and pyroptosis. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-14 Kateryna Shkarina,Eva Hasel de Carvalho,José Carlos Santos,Saray Ramos,Maria Leptin,Petr Broz
Targeted and specific induction of cell death in an individual or groups of cells hold the potential for new insights into the response of tissues or organisms to different forms of death. Here, we report the development of optogenetically controlled cell death effectors (optoCDEs), a novel class of optogenetic tools that enables light-mediated induction of three types of programmed cell death (PCD)-apoptosis
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TRPC3 channel gating by lipids requires localization at the ER/PM junctions defined by STIM1. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-13 Haiping Liu,Wei-Yin Lin,Spencer R Leibow,Alexander J Morateck,Malini Ahuja,Shmuel Muallem
TRPC3, a member of the transient receptor potential (TRP) superfamily of cation channels, is a lipid-regulated, Ca2+-permeable channel that mediates essential components of the receptor evoked Ca2+ signal. The modes and mechanisms by which lipids regulate TRPC3 and other members of the TRPC channel family are not well understood. Here, we report that PI(4,5)P2 regulates TRPC3 in three independent modes
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An unexpected role for PD-L1 in front-rear polarization and directional migration. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-13 Miguel Sánchez-Álvarez,Miguel A Del Pozo
Programmed cell death-ligand 1 (PD-L1)-mediated T cell inhibition through PD-1 is a key checkpoint frequently exploited by tumors to evade immunity. In this issue, Wang et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202108083) reveal an unexpected role for PD-L1 in promoting tumor cell front-rear polarity and directionally persistent cell migration, independently of PD-1.
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Synaptopodin stress fiber and contractomere at the epithelial junction. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-13 Timothy Morris,Eva Sue,Caleb Geniesse,William M Brieher,Vivian W Tang
The apical junction of epithelial cells can generate force to control cell geometry and perform contractile processes while maintaining barrier function and adhesion. Yet, the structural basis for force generation at the apical junction is not fully understood. Here, we describe two synaptopodin-dependent actomyosin structures that are spatially, temporally, and structurally distinct. The first structure
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Actomyosin activity-dependent apical targeting of Rab11 vesicles reinforces apical constriction J. Cell Biol. (IF 10.539) Pub Date : 2022-04-11 Wei Chen,Bing He
During tissue morphogenesis, the changes in cell shape, resulting from cell-generated forces, often require active regulation of intracellular trafficking. How mechanical stimuli influence intracellular trafficking and how such regulation impacts tissue mechanics are not fully understood. In this study, we identify an actomyosin-dependent mechanism involving Rab11-mediated trafficking in regulating
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The HOPS tethering complex is required to maintain signaling endosome identity and TORC1 activity. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-09 Jieqiong Gao,Raffaele Nicastro,Marie-Pierre Péli-Gulli,Sophie Grziwa,Zilei Chen,Rainer Kurre,Jacob Piehler,Claudio De Virgilio,Florian Fröhlich,Christian Ungermann
The endomembrane system of eukaryotic cells is essential for cellular homeostasis during growth and proliferation. Previous work showed that a central regulator of growth, namely the target of rapamycin complex 1 (TORC1), binds both membranes of vacuoles and signaling endosomes (SEs) that are distinct from multivesicular bodies (MVBs). Interestingly, the endosomal TORC1, which binds membranes in part
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Establishing spatial control over TORC1 signaling. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-09 Oliver Schmidt,Mariana E G de Araujo
Target-of-rapamycin complex 1 resides on lysosomes/vacuoles and additionally on signaling endosomes. Gao et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202109084) set out to define the molecular identity of signaling endosomes, along with players required for the formation and maintenance of this endosomal subpopulation.
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CPAP insufficiency leads to incomplete centrioles that duplicate but fragment. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-09 Alejandra Vásquez-Limeta,Kimberly Lukasik,Dong Kong,Catherine Sullenberger,Delgermaa Luvsanjav,Natalie Sahabandu,Raj Chari,Jadranka Loncarek
Centrioles are structures that assemble centrosomes. CPAP is critical for centrosome assembly, and its mutations are found in patients with diseases such as primary microcephaly. CPAP's centrosomal localization, its dynamics, and the consequences of its insufficiency in human cells are poorly understood. Here we use human cells genetically engineered for fast degradation of CPAP, in combination with
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MOSPD2 is an endoplasmic reticulum–lipid droplet tether functioning in LD homeostasis J. Cell Biol. (IF 10.539) Pub Date : 2022-04-07 Mehdi Zouiouich,Thomas Di Mattia,Arthur Martinet,Julie Eichler,Corinne Wendling,Nario Tomishige,Erwan Grandgirard,Nicolas Fuggetta,Catherine Fromental-Ramain,Giulia Mizzon,Calvin Dumesnil,Maxime Carpentier,Bernardo Reina-San-Martin,Carole Mathelin,Yannick Schwab,Abdou Rachid Thiam,Toshihide Kobayashi,Guillaume Drin,Catherine Tomasetto,Fabien Alpy
Membrane contact sites between organelles are organized by protein bridges. Among the components of these contacts, the VAP family comprises ER–anchored proteins, such as MOSPD2, that function as major ER–organelle tethers. MOSPD2 distinguishes itself from the other members of the VAP family by the presence of a CRAL-TRIO domain. In this study, we show that MOSPD2 forms ER–lipid droplet (LD) contacts
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DAPLE orchestrates apical actomyosin assembly from junctional polarity complexes. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-07 Arthur Marivin,Rachel Xi-Yeen Ho,Mikel Garcia-Marcos
Establishment of apicobasal polarity and the organization of the cytoskeleton must operate coordinately to ensure proper epithelial cell shape and function. However, the precise molecular mechanisms by which polarity complexes directly instruct the cytoskeletal machinery to determine cell shape are poorly understood. Here, we define a mechanism by which the PAR polarity complex (PAR3-PAR6-aPKC) at
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Filling in the gaps: SNX-RGS proteins as multiorganelle tethers. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-07 Hanaa Hariri,W Mike Henne
SNX-RGS proteins are molecular tethers localized to multiple interorganelle contact sites that exhibit roles in cellular metabolism. Here, we highlight recent findings on these proteins and discuss their emerging roles in metabolism, human disease, and lipid trafficking.
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Filament organization of the bacterial actin MreB is dependent on the nucleotide state. J. Cell Biol. (IF 10.539) Pub Date : 2022-04-04 Vani Pande,Nivedita Mitra,Saket Rahul Bagde,Ramanujam Srinivasan,Pananghat Gayathri
MreB, the bacterial ancestor of eukaryotic actin, is responsible for shape in most rod-shaped bacteria. Despite belonging to the actin family, the relevance of nucleotide-driven polymerization dynamics for MreB function is unclear. Here, we provide insights into the effect of nucleotide state on membrane binding of Spiroplasma citri MreB5 (ScMreB5). Filaments of ScMreB5WT and an ATPase-deficient mutant
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Structural and biochemical insights into lipid transport by VPS13 proteins J. Cell Biol. (IF 10.539) Pub Date : 2022-03-31 Jyoti Adlakha,Zhouping Hong,PeiQi Li,Karin M. Reinisch
VPS13 proteins are proposed to function at contact sites between organelles as bridges for lipids to move directionally and in bulk between organellar membranes. VPS13s are anchored between membranes via interactions with receptors, including both peripheral and integral membrane proteins. Here we present the crystal structure of VPS13s adaptor binding domain (VAB) complexed with a Pro-X-Pro peptide
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Three interacting regions of the Ndc80 and Dam1 complexes support microtubule tip-coupling under load. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-30 Rachel L Flores,Zachary E Peterson,Alex Zelter,Michael Riffle,Charles L Asbury,Trisha N Davis
Accurate mitosis requires kinetochores to make persistent, load-bearing attachments to dynamic microtubule tips, thereby coupling chromosome movements to tip growth and shortening. This tip-coupling behavior depends on the conserved Ndc80 complex and, in budding yeast, on the Dam1 complex, which bind each other directly via three distinct interacting regions. The functional relevance of these multiple
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PD-LI promotes rear retraction during persistent cell migration by altering integrin β4 dynamics. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-28 Mengdie Wang,Choua Xiong,Arthur M Mercurio
Although the immune checkpoint function of PD-L1 has dominated its study, we report that PD-L1 has an unanticipated intrinsic function in promoting the dynamics of persistent cell migration. PD-L1 concentrates at the rear of migrating carcinoma cells where it facilitates retraction, resulting in the formation of PD-L1-containing retraction fibers and migrasomes. PD-L1 promotes retraction by interacting
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Non-canonical ubiquitylation makes its mark on Rap2 and cell motility. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-25 Patrick T Caswell
Ubiquitin modification controls protein stability and cargo trafficking, and in this issue Duncan et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202107114) reveal a unique mechanism through which Rab40b/Cul5-mediated ubiquitylation of Rap2 regulates its activity and recycling to the leading edge to control cell migration and invasion.
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Dia1 coordinates differentiation and cell sorting in a stratified epithelium J. Cell Biol. (IF 10.539) Pub Date : 2022-03-24 Robert M. Harmon,John Devany,Margaret L. Gardel
Although implicated in adhesion, only a few studies address how the actin assembly factors guide cell positioning in multicellular tissues. The formin, Dia1, localizes to the proliferative basal layer of the epidermis. In organotypic cultures, Dia1 depletion reduced basal cell density and resulted in stratified tissues with disorganized differentiation and proliferative markers. Since crowding induces
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Local regulation of extracellular vesicle traffic by the synaptic endocytic machinery J. Cell Biol. (IF 10.539) Pub Date : 2022-03-23 Cassandra R. Blanchette,Amy L. Scalera,Kathryn P. Harris,Zechuan Zhao,Erica C. Dresselhaus,Kate Koles,Anna Yeh,Julia K. Apiki,Bryan A. Stewart,Avital A. Rodal
Neuronal extracellular vesicles (EVs) are locally released from presynaptic terminals, carrying cargoes critical for intercellular signaling and disease. EVs are derived from endosomes, but it is unknown how these cargoes are directed to the EV pathway rather than for conventional endolysosomal degradation. Here, we find that endocytic machinery plays an unexpected role in maintaining a release-competent
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Clathrin coated pits as signaling platforms for Akt signaling. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-23 Elizabeth Smythe
Signaling by the activated epidermal growth factor receptor (EGFR) results in diverse cell fates. In this issue, Cabral-Dias et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.201808181) demonstrate how plasma membrane clathrin coated pits can act as a signaling platform for one branch of EGFR downstream signaling.
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mTORC2 suppresses cell death induced by hypo-osmotic stress by promoting sphingomyelin transport. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-23 Yumiko Ono,Kenji Matsuzawa,Junichi Ikenouchi
Epithelial cells are constantly exposed to osmotic stress. The influx of water molecules into the cell in a hypo-osmotic environment increases plasma membrane tension as it rapidly expands. Therefore, the plasma membrane must be supplied with membrane lipids since expansion beyond its elastic limit will cause the cell to rupture. However, the molecular mechanism to maintain a constant plasma membrane
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Ori Avinoam: Mind, body, and membranes in shape. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-23 Lucia Morgado-Palacin
Ori Avinoam studies membrane remodeling with a focus on cell-to-cell fusion through the lens of correlative light and electron microscopy.
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Tweaking neural organoids to model human reactive astrocytes. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-23 Paola Bezzi
The study of human reactive astrocytes has been limited by resource availability. In this issue, Cvetkovic et al. (2022. J. Cell Biol.https://doi.org/10.1083/jcb.202107135) develop multicellular organoid systems containing mature astrocytes to study the dynamics of human astrocytes reactivity and its downstream effects on neuronal activity.
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Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration J. Cell Biol. (IF 10.539) Pub Date : 2022-03-16 Emily D. Duncan,Ke-Jun Han,Margaret A. Trout,Rytis Prekeris
Cell migration is a complex process that involves coordinated changes in membrane transport and actin cytoskeleton dynamics. Ras-like small monomeric GTPases, such as Rap2, play a key role in regulating actin cytoskeleton dynamics and cell adhesions. However, how Rap2 function, localization, and activation are regulated during cell migration is not fully understood. We previously identified the small
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A JAM-A-tetraspanin-αvβ5 integrin complex regulates contact inhibition of locomotion. J. Cell Biol. (IF 10.539) Pub Date : 2022-03-16 Daniel Kummer,Tim Steinbacher,Sonja Thölmann,Mariel Flavia Schwietzer,Christian Hartmann,Simone Horenkamp,Sabrina Demuth,Swetha S D Peddibhotla,Frauke Brinkmann,Björn Kemper,Jürgen Schnekenburger,Matthias Brandt,Timo Betz,Ivan Liashkovich,Ivan U Kouzel,Victor Shahin,Nathalie Corvaia,Klemens Rottner,Katsiaryna Tarbashevich,Erez Raz,Lilo Greune,M Alexander Schmidt,Volker Gerke,Klaus Ebnet
Contact inhibition of locomotion (CIL) is a process that regulates cell motility upon collision with other cells. Improper regulation of CIL has been implicated in cancer cell dissemination. Here, we identify the cell adhesion molecule JAM-A as a central regulator of CIL in tumor cells. JAM-A is part of a multimolecular signaling complex in which tetraspanins CD9 and CD81 link JAM-A to αvβ5 integrin