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Dev Cell. 2019 Nov 18;51(4):476-487.e7. doi: 10.1016/j.devcel.2019.10.018.

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

Author information

1
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.
2
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany; Graduate School of Quantitative Biosciences Munich, Munich 81337, Germany.
3
ICFO, Institut de Ciencies Fotoniques, The Barcelona Institute of Science and Technology, Castelldefels 08860, Spain.
4
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland.
5
MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
6
Department of Molecular Biology, University of Geneva, Geneva 1211, Switzerland; Swiss National Centre for Competence in Research, Program Chemical Biology, Geneva 1211, Switzerland.
7
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, Martinsried 82152, Germany.
8
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. Electronic address: ruben.fernandezbusnadiego@med.uni-goettingen.de.

Abstract

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.

KEYWORDS:

cryo-ET; cryo-FIB; cryo-electron tomography; cryo-focused ion beam milling; endoplasmic reticulum; membrane contact site; membrane curvature; plasma membrane; tricalbins

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