Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity

Anjali Verma, Resham Bhattacharya, Indu Remadevi, Keguo Li, Kallal Pramanik, Ganesh V. Samant, Mark Horswill, Chang Z. Chun, Baofeng Zhao, Enfeng Wang, Robert Qing Miao, Debabrata Mukhopadhyay, Ramani Ramchandran, George A. Wilkinson

Research output: Contribution to journalArticle

23 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)4614-4622
Number of pages9
JournalBlood
Volume115
Issue number22
DOIs
StatePublished - Jun 3 2010

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Verma, A., Bhattacharya, R., Remadevi, I., Li, K., Pramanik, K., Samant, G. V., Horswill, M., Chun, C. Z., Zhao, B., Wang, E., Miao, R. Q., Mukhopadhyay, D., Ramchandran, R., & Wilkinson, G. A. (2010). Endothelial cell-specific chemotaxis receptor (ecscr) promotes angioblast migration during vasculogenesis and enhances VEGF receptor sensitivity. Blood, 115(22), 4614-4622. https://doi.org/10.1182/blood-2009-10-248856