Rab10 Promotes Atlastin‐Mediated Endoplasmic Reticulum Membrane Fusion

ABSTRACT

Intracellular membrane fusion typically involves two distinct classes of GTPases. Dynamin‐like GTPases mediate homotypic fusion between organelles, such as mitochondria and the endoplasmic reticulum (ER), while Rab GTPases facilitate fusion of transport vesicles with target membranes through vesicle tethering. Notably, these two classes of GTPases have not previously been implicated in the same fusion event. In this study, we demonstrate that Rab10 promotes ER membrane fusion driven by the dynamin‐like GTPase atlastin (ATL). Rab10 interacted physically with ATL2, a human ATL predominantly expressed in non‐neuronal cells, and co‐localized with ATL2 throughout the ER, including at three‐way junctions where fusion occurs. Fusion between ER microsomes isolated from HEK293T cells, in which ATL2 is the primary ATL isoform, was inhibited by affinity‐purified anti‐Rab10 antibodies, and was reduced in microsomes derived from Rab10 knockout cells. Moreover, co‐reconstitution of Rab10 markedly enhanced fusion of ATL2‐containing liposomes. Our findings reveal crosstalk between dynamin‐like and Rab GTPases during ATL‐mediated ER membrane fusion, uncovering a novel regulatory mechanism for organelle dynamics.