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Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity. Blood 2010 Jun 03;115(22):4614-22

Date

01/21/2010

Pubmed ID

20086248

Pubmed Central ID

PMC2881497

DOI

10.1182/blood-2009-10-248856

Abstract

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.

Author List

Verma A, Bhattacharya R, Remadevi I, Li K, Pramanik K, Samant GV, Horswill M, Chun CZ, Zhao B, Wang E, Miao RQ, Mukhopadhyay D, Ramchandran R, Wilkinson GA

Author

Ramani Ramchandran PhD Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Animals
Apoptosis
Base Sequence
Blood Vessels
Cell Movement
Cell Proliferation
Cells, Cultured
Chemotaxis
DNA Primers
Endothelial Cells
Gene Expression Regulation, Developmental
Gene Knockdown Techniques
Humans
Membrane Proteins
Recombinant Proteins
Signal Transduction
Transfection
Vascular Endothelial Growth Factor Receptor-2
Zebrafish
Zebrafish Proteins
jenkins-FCD Prod-484 8aa07fc50b7f6d102f3dda2f4c7056ff84294d1d