The Neuropilin 1 Cytoplasmic Domain Is Required for VEGF-A-Dependent Arteriogenesis

• DOI: 10.1016/j.devcel.2013.03.019
• Publication Date: 2013-04-29T15:16:31Z
• Authors: Anthony Lanahan; Xi Zhang; Alessandro Fantin; Zhen Zhuang; Felix Rivera-Molina; Katherine Speichi...; Claudia Prahst; Jiasheng Zhang; Yingdi Wang; George Davis; Derek Toomre; Christiana Ruhrberg; Michael Simons
• Keywords: PDZ domain; Neuropilin; Arteriogenesis

Neuropilin 1 (NRP1) plays an important but ill-defined role in VEGF-A signaling and vascular morphogenesis. We show that mice with a knockin mutation ablates the NRP1 cytoplasmic tail (Nrp1cyto) have normal angiogenesis impaired developmental adult arteriogenesis. The arteriogenic defect was traced to absence of PDZ-dependent interaction between VEGF receptor 2 (VEGFR2) complex synectin, which delayed trafficking endocytosed VEGFR2 from Rab5+ EAA1+ endosomes. This led increased PTPN1 (PTP1b)-mediated dephosphorylation at Y1175, site involved activating ERK signaling. Nrp1cyto also endothelial tubulogenesis vitro, could be rescued by expressing full-length or constitutively active ERK. These results demonstrate domain promotes manner regulate establish for during