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

62 Pages Posted: 16 Apr 2019 Sneak Peek Status: Under Review

See all articles by Javier Collado

Javier Collado

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Maria Kalemanov

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Antonio Martinez-Sanchez

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Felix Campelo

The Barcelona Institute of Science and Technology (BIST) - Institute of Photonic Sciences (ICFO)

Wolfgang Baumeister

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Christopher J. Stefan

University College London - MRC LMCB - Laboratory for Molecular Cell Biology

Ruben Fernandez-Busnadiego

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

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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 S. 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. In particular, Tcb proteins form peaks of extreme curvature on the cER membrane facing the PM. Semi-quantitative modeling and functional assays suggest that Tcb-mediated cER peaks facilitate the transport of lipids from the cER to the PM, necessary to maintain PM integrity under stress conditions. ER peaks were also present at other MCS, implying that membrane curvature enforcement may be a widespread mechanism to expedite lipid transport at MCS.

Keywords: Membrane contact site, endoplasmic reticulum, plasma membrane, tricalbins, membrane curvature, cryo‐electron tomography

Suggested Citation

Collado, Javier and Kalemanov, Maria and Martinez-Sanchez, Antonio and Campelo, Felix and Baumeister, Wolfgang and Stefan, Christopher J. and Fernandez-Busnadiego, Ruben, Tricalbin-Mediated Contact Sites Control ER Curvature to Maintain Plasma Membrane Integrity (April 13, 2019). Available at SSRN: https://ssrn.com/abstract=3371409 or http://dx.doi.org/10.2139/ssrn.3371409
This is a paper under consideration at Cell Press and has not been peer-reviewed.

Javier Collado

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Am Klopferspitz 18
Martinsried, 82152
Germany

Maria Kalemanov

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Am Klopferspitz 18
Martinsried, 82152
Germany

Antonio Martinez-Sanchez

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Am Klopferspitz 18
Martinsried, 82152
Germany

Felix Campelo

The Barcelona Institute of Science and Technology (BIST) - Institute of Photonic Sciences (ICFO)

Spain

Wolfgang Baumeister

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology

Am Klopferspitz 18
Martinsried, 82152
Germany

Christopher J. Stefan

University College London - MRC LMCB - Laboratory for Molecular Cell Biology

Gower St
Kings Cross
London, WC1E 6BT
United Kingdom

Ruben Fernandez-Busnadiego (Contact Author)

Max Planck Institute of Biochemistry - Department of Molecular Structural Biology ( email )

Am Klopferspitz 18
Martinsried, 82152
Germany

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