Mechanism of membrane-curvature generation by ER-tubule shaping proteins

Ning Wang, Lindsay D. Clark, Yuan Gao, Michael M. Kozlov, Tom Shemesh and Tom A. Rapoport ()
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Ning Wang: Harvard Medical School
Lindsay D. Clark: Harvard Medical School
Yuan Gao: Harvard Medical School
Michael M. Kozlov: Sackler Faculty of Medicine, Tel Aviv University
Tom Shemesh: Technion-Israel Institute of Technology
Tom A. Rapoport: Harvard Medical School

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The endoplasmic reticulum (ER) network consists of tubules with high membrane curvature in cross-section, generated by the reticulons and REEPs. These proteins have two pairs of trans-membrane (TM) segments, followed by an amphipathic helix (APH), but how they induce curvature is poorly understood. Here, we show that REEPs form homodimers by interaction within the membrane. When overexpressed or reconstituted at high concentrations with phospholipids, REEPs cause extreme curvature through their TMs, generating lipoprotein particles instead of vesicles. The APH facilitates curvature generation, as its mutation prevents ER network formation of reconstituted proteoliposomes, and synthetic L- or D-amino acid peptides abolish ER network formation in Xenopus egg extracts. In Schizosaccharomyces japonicus, the APH is required for reticulon’s exclusive ER-tubule localization and restricted mobility. Thus, the TMs and APH cooperate to generate high membrane curvature. We propose that the formation of splayed REEP/reticulon dimers is responsible for ER tubule formation.

Date: 2021
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DOI: 10.1038/s41467-020-20625-y

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