The study of Rab GTPase mediated regulation of the endoplasmic reticulum structure

Abstract

The intricate mesh-like structure of endoplasmic reticulum (ER) tubules is maintained by homotypic membrane fusion between ER tubules, mediated by the evolutionarily conserved dynamin-like GTPase, atlastin. Although a subset of Rab proteins, another family of GTPases, has been implicated in regulating ER structure, the relationship between atlastins and Rab GTPases in ER fusion remains unclear. This study reveals that Rab10, a Rab GTPase previously reported to regulate ER structure, participates in the atlastin-mediated ER fusion pathway. We demonstrate that Rab10 physically interacts with ATL2, a human atlastin protein predominantly expressed in non-neuronal cells. Fusion between ER microsomes isolated from HEK293 cells, where ATL2 is the major atlastin, is inhibited by anti-Rab10 antibodies. Furthermore, the co-reconstitution of Rab10 into liposomes markedly enhances the fusion of ATL2-containing liposomes. Our findings suggest that Rab10 functions as a crucial regulator of ATL2-mediated ER membrane fusion.