Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity.,Developmental Cell

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Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity.
Developmental Cell ( IF 10.7 ) Pub Date : 2019-11-18 , DOI: 10.1016/j.devcel.2019.10.018
Javier Collado ₁ , Maria Kalemanov ₂ , Felix Campelo ₃ , Clélia Bourgoint ₄ , Ffion Thomas ₅ , Robbie Loewith ₆ , Antonio Martínez-Sánchez ₇ , Wolfgang Baumeister ₇ , Christopher J Stefan ₅ , Rubén Fernández-Busnadiego ₈

Affiliation

Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Institute of Neuropathology, University Medical Center Göttingen, Göttingen 37099, Germany; Graduate School of Quantitative Biosciences Munich, Munich 81337, Germany.
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Graduate School of Quantitative Biosciences Munich, Munich 81337, Germany.
ICFO, Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Castelldefels 08860, Spain.
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.
MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland; Swiss National Centre for Competence in Research, Program Chemical Biology, Geneva 1211, Switzerland.
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Institute of Neuropathology, University Medical Center Göttingen, Göttingen 37099, Germany; Cluster of Excellence "Multiscale Bioimaging: from Molecular Machines to Networks of Excitable Cells" (MBExC), University of Göttingen, Göttingen, Germany.

Membrane contact sites (MCS) between the endoplasmic reticulum (ER) and the plasma membrane (PM) play fundamental roles in all eukaryotic cells. ER-PM MCS are particularly abundant in Saccharomyces cerevisiae, where approximately half of the PM surface is covered by cortical ER (cER). Several proteins, including Ist2, Scs2/22, and Tcb1/2/3 are implicated in cER formation, but the specific roles of these molecules are poorly understood. Here, we use cryo-electron tomography to show that ER-PM tethers are key determinants of cER morphology. Notably, Tcb proteins (tricalbins) form peaks of extreme curvature on the cER membrane facing the PM. Combined modeling and functional assays suggest that Tcb-mediated cER peaks facilitate the transport of lipids between the cER and the PM, which is necessary to maintain PM integrity under heat stress. ER peaks were also present at other MCS, implying that membrane curvature enforcement may be a widespread mechanism to regulate MCS function.

中文翻译：

Tricalbin 介导的接触位点控制 ER 曲率以维持质膜完整性。

内质网 (ER) 和质膜 (PM) 之间的膜接触位点 (MCS) 在所有真核细胞中发挥着重要作用。ER-PM MCS 在酿酒酵母中特别丰富，其中大约一半的 PM 表面被皮质 ER (cER) 覆盖。包括 Ist2、Scs2/22 和 Tcb1/2/3 在内的多种蛋白质与 cER 形成有关，但人们对这些分子的具体作用知之甚少。在这里，我们使用冷冻电子断层扫描来证明 ER-PM 系链是 cER 形态的关键决定因素。值得注意的是，Tcb 蛋白（三卡宾）在面向 PM 的 cER 膜上形成极端曲率的峰。联合建模和功能测定表明，Tcb 介导的 cER 峰促进 cER 和 PM 之间的脂质转运，这对于在热应激下维持 PM 完整性是必要的。ER 峰也存在于其他 MCS 中，这意味着膜曲率强制可能是调节 MCS 功能的广泛机制。

更新日期：2019-11-18

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