Scientific Publications
Neuropilin 1 and Neuropilin 2 direct a5 integrin trafficking through GTPase-activating-protein p120RasGAP in endothelial cells to promote fibronectin fibrillogenesis
Nature Communications Biology
Integrin trafficking to and from membrane adhesions is a crucial mechanism that dictates many aspects of a cells behaviour, including motility, polarisation, and invasion. In endothelial cells (ECs), the intracellular trafficking of a5 integrin is regulated by both neuropilin 1 (NRP1) and neuropilin 2 (NRP2), yet the redundancies in function between these co-receptors remain unclear. Moreover, the endocytic complexes that participate in NRP-directed trafficking remain poorly annotated. Here we identify an important role for the GTPase-activating protein p120RasGAP in ECs, promoting the recycling of a5 integrin from early endosomes. Mechanistically, p120RasGAP enables transit of endocytosed a5 integrin-NRP1-NRP2 complexes to Rab11+ recycling endosomes, promoting cell polarisation and fibronectin (FN) fibrillogenesis. Silencing of both NRP receptors, or p120RasGAP, resulted in the accumulation of a5 integrin in early endosomes, a loss of a5 integrin from surface adhesions, and attenuated EC polarisation. Endothelial-specific deletion of both NRP1 and NRP2 in the postnatal retina recapitulated our in vitro findings, severely impairing FN fibrillogenesis and polarised sprouting. Our data assign an essential role for p120RasGAP during integrin trafficking in ECs and support a hypothesis that NRP receptors co-traffic internalised cargoes.
Nature Communications Biology
View Publication
