| First Author | Lanahan AA | Year | 2010 |
| Journal | Dev Cell | Volume | 18 |
| Issue | 5 | Pages | 713-24 |
| PubMed ID | 20434959 | Mgi Jnum | J:160132 |
| Mgi Id | MGI:4453490 | Doi | 10.1016/j.devcel.2010.02.016 |
| Citation | Lanahan AA, et al. (2010) VEGF receptor 2 endocytic trafficking regulates arterial morphogenesis. Dev Cell 18(5):713-24 |
| abstractText | VEGF is the key growth factor regulating arterial morphogenesis. However, molecular events involved in this process have not been elucidated. Synectin null mice demonstrate impaired VEGF signaling and a marked reduction in arterial morphogenesis. Here, we show that this occurs due to delayed trafficking of VEGFR2-containing endosomes that exposes internalized VEGFR2 to selective dephosphorylation by PTP1b on Y(1175) site. Synectin involvement in VEGFR2 intracellular trafficking requires myosin-VI, and myosin-VI knockout in mice or knockdown in zebrafish phenocopy the synectin null phenotype. Silencing of PTP1b restores VEGFR2 activation and significantly recovers arterial morphogenesis in myosin-VI(-/-) knockdown zebrafish and synectin(-/-) mice. We conclude that activation of the VEGF-mediated arterial morphogenesis cascade requires phosphorylation of the VEGFR2 Y(1175) site that is dependent on trafficking of internalized VEGFR2 away from the plasma membrane via a synectin-myosin-VI complex. This key event in VEGF signaling occurs at an intracellular site and is regulated by a novel endosomal trafficking-dependent process. |
