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The myosin motor Myo1c is required for VEGF‐induced VEGFR2 delivery to the cell surface and angiogenic signaling
Author(s) -
Choudhury Amit
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.526.1
Subject(s) - microbiology and biotechnology , biology , kinase insert domain receptor , myosin , endocytic cycle , signal transduction , angiogenesis , phosphorylation , tyrosine kinase , vascular endothelial growth factor a , receptor , vascular endothelial growth factor , endocytosis , vegf receptors , cancer research , biochemistry
Vascular endothelial growth factor receptor‐2 (VEGFR2) is a receptor tyrosine kinase expressed in endothelial cells and regulates angiogenic signal transduction processes during physiological and pathological conditions. Intracellular vesicular transport of VEGFR2 along endocytic and secretory transport pathways regulates turnover of this receptor at the plasma membrane (PM). Motor proteins of the myosin family regulate short range cargo trafficking along actin filaments. In the current study using primary human endothelial cells, we demonstrate that Myo1c, an unconventional class I myosin, regulates the availability of VEGFR2 at the PM. Myo1c co‐localizes with VEGFR2 and caveolin‐1 (Cav1) at the PM. VEGFR2 recruitment, and co‐localization with Myo1c and Cav1 at the PM occurs in response to VEGF‐A stimulation. Depletion of Myo1c reduces total and cell surface VEGFR2 that could be rescued by overexpression of wild type form of Myo1c. VEGF‐induced VEGFR2 delivery to the PM requires Myo1c, as depletion of Myo1c targets the receptor to the lysosomes for degradation. Depletion of Myo1c reduces VEGFR2 phosphorylation at Y1175 and also reduced activation of ERK1/2 and c‐Src that leads to reduced cell proliferation and cell migration, respectively, in response to VEGF. This study is the first report showing Myo1c as an important player for VEGF‐induced VEGFR2 delivery to the PM and angiogenic signaling.