Rab35 drives epidermal wound closure by promoting lamellipodial protrusions and membrane vesicle transport

Abstract

In response to tissue damage, the epidermal barrier must be restored immediately to prevent excessive blood loss and infections. How cells coordinate actin-driven protrusions and membrane transport during reepithelialization is poorly understood. Here, we identified Rab35 as an important driver of epidermal wound closure in Drosophila. Endogenous Rab35 positive vesicles are directed to the wound edge and in protruding lamellipodia. Suppression of Rab35 function results in striking lamellipodia defects and an accumulation of PIP2-positive vesicles. Depletion of Fascin, a known Rab35 effector phenocopies rab35 knockdown. Upstream of Rab35, we identified CG18659 as potential Rab35-GEF protein, which physically interacts and colocalizes with Rab35. Suppression of Rab35 GEF CG18659 or overexpression of Rab35 GAP Whacked results in strong wound healing defects. We propose model in which Rab35 drives epidermal wound closure by promoting Fascin-stabilized actin-driven protrusions and vesicle transport required for cell membrane expansion and local PIP2 delivery at the wound site.