Title: VEGF Receptor 2 Endocytic Trafficking Regulates Arterial Morphogenesis
Authors: Lanahan, Anthony A
Hermans, Karlien
Claes, Filip
Kerley-Hamilton, Joanna S
Zhuang, Zhen W
Giordano, Frank J
Carmeliet, Peter
Simons, Michael # ×
Issue Date: Apr-2010
Publisher: Cell Press
Series Title: Developmental Cell vol:18 issue:5 pages:713-724
Abstract: 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.
ISSN: 1534-5807
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Vesalius Research Centre (-)
Division of Gene Technology (-)
Laboratory of Angiogenesis and Vascular Metabolism (Vesalius Research Center) (+)
Switch Laboratory
× corresponding author
# (joint) last author

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