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Nat Commun 2021 Jan 25;121:568. doi: 10.1038/s41467-020-20625-y.
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Mechanism of membrane-curvature generation by ER-tubule shaping proteins.

Wang N , Clark LD , Gao Y , Kozlov MM , Shemesh T , Rapoport TA .

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.

PubMed ID: 33495454
PMC ID: PMC7835363
Article link: Nat Commun
Grant support: [+]

Species referenced: Xenopus laevis
Genes referenced: mtor ncr3 reep1 rtn1
GO keywords: endoplasmic reticulum

Article Images: [+] show captions
References [+] :
Aoki, Novel episomal vectors and a highly efficient transformation procedure for the fission yeast Schizosaccharomyces japonicus. 2010, Pubmed