Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity.
Endothelial cell-specific chemotaxis receptor (ECSCR) is a cell surface protein expressed by blood endothelial cells with roles in endothelial cell migration and signal transduction. We investigated the function of ecscr in the development of the zebrafish vasculature. Zebrafish ecscr is expressed in angioblasts and in axial vessels during angioblast migration and vasculogenesis. Morpholino-directed ecscr knockdown resulted in defective angioblast migration in the posterior lateral plate mesoderm, a process known to depend on vascular endothelial-derived growth factor (VEGF). In cultured cells, transfected ECSCR localized to actin-rich membrane protrusions, colocalizing with kinase insert domain protein receptor (KDR)/VEGF receptor 2 in these regions. ECSCR-silenced cells show reduced VEGF-induced phosphorylation of KDR but not of FMS-like tyrosine kinase 1 (FLT1)/VEGF receptor 1. Finally, chemical inhibition of VEGF receptor activity in zebrafish resulted in angioblast deficiencies that partially overlap with those seen in ecscr morphants. We propose that ecscr promotes migration of zebrafish angioblasts by enhancing endothelial kdr sensitivity to VEGF.
Verma
Anjali
A
Department of Pediatrics and Developmental Vascular Biology Program, Medical College of Wisconsin and Children's Research Institute, Milwaukee, WI 53226, USA.
Bhattacharya
Resham
R
Remadevi
Indu
I
Li
Keguo
K
Pramanik
Kallal
K
Samant
Ganesh V
GV
Horswill
Mark
M
Chun
Chang Z
CZ
Zhao
Baofeng
B
Wang
Enfeng
E
Miao
Robert Qing
RQ
Mukhopadhyay
Debabrata
D
Ramchandran
Ramani
R
Wilkinson
George A
GA
D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D001483:Base Sequence; D001808:Blood Vessels / Q000196:embryology* / Q000378:metabolism*; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D002633:Chemotaxis / Q000502:physiology*; D017931:DNA Primers / Q000235:genetics; D042783:Endothelial Cells / Q000378:metabolism; D018507:Gene Expression Regulation, Developmental; D055785:Gene Knockdown Techniques; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D014162:Transfection; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D015027:Zebrafish / Q000196:embryology* / Q000235:genetics / Q000378:metabolism*; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
D051017:Apoptosis Regulatory Proteins; D017931:DNA Primers; C531407:ECSCR protein, human; D008565:Membrane Proteins; D011994:Recombinant Proteins; D029961:Zebrafish Proteins; D040301:Vascular Endothelial Growth Factor Receptor-2