The Rab-effector protein RABEP2 regulates endosomal trafficking to mediate vascular endothelial growth factor receptor-2 (VEGFR2)-dependent signaling

• DOI: 10.1074/jbc.m117.812172
• Publication Date: 2018-02-07T21:10:12Z
• Authors: Natalie Kofler; Federico Corti; Felix Rivera-Molina; Yong Deng; Derek Toomre; Michael Simons
• Keywords: Rab

As a master regulator of endothelial cell function, vascular growth factor receptor-2 (VEGFR2) activates multiple downstream signaling pathways that are critical for development and normal vessel function. VEGFR2 trafficking through various endosomal compartments modulates its output. Accordingly, proteins regulate the speed direction by which traffics endosomes have been demonstrated to be particularly important arteriogenesis. However, little is known about how these control implications this Here, we show Rab GTPase–binding effector protein 2 (RABEP2), Rab-effector implicated in arteriogenesis, trafficking. By employing high-resolution microscopy biochemical assays, demonstrate RABEP2 interacts with small GTPase Rab4 regulates maintain cell-surface expression VEGF signaling. Lack also led prolonged retention Rab5-positive sorting endosomes, increased VEGFR2's exposure phosphotyrosine phosphatase 1b (PTP1b), causing diminished Finally, loss degradation diverting Rab7-positive destined lysosome. These results implicate as key modulator trafficking, importance cells.