Isolation of a small vasohibin-binding protein (SVBP) and its role in vasohibin secretion

Yasuhiro Suzuki, Miho Kobayashi, Hiroki Miyashita, Hideki Ohta, Hikaru Sonoda, Yasufumi Sato

Research output: Contribution to journalArticlepeer-review

42 Citations (Scopus)

Abstract

Upon stimulation with angiogenic factors, vascular endothelial cells (ECs) secrete a negative-feedback regulator of angiogenesis, vasohibin-1 (VASH1). Because VASH1 lacks a classical signal sequence, it is not clear how ECs secrete VASH1. We isolated a small vasohibin-binding protein (SVBP) composed of 66 amino acids. The level of Svbp mRNA was relatively high in the bone marrow, spleen and testes of mice. In cultured ECs, Vash1 mRNA was induced by VEGF, and Svbp mRNA was expressed constitutively. The interaction between VASH1 and SVBP was confirmed using the BIAcore system and immunoprecipitation analysis. Immunocytochemical analysis revealed that SVBP colocalized with VASH1 in ECs. In polarized epithelial cells, SVBP accumulated on the apical side, whereas VASH1 was present throughout the cells and partially colocalized with SVBP. Transfection of SVBP enhanced VASH1 secretion, whereas knockdown of endogenous SVBP markedly reduced VASH1 secretion. SVBP increased the solubility of VASH1 protein in detergent solution and inhibited the ubiquitylation of VASH1 protein. Moreover, co-transfection of SVBP significantly augmented the inhibitory effect of VASH1 on EC migration. These results indicate that SVBP acts as a secretory chaperone for VASH1 and contributes to the anti-angiogenic activity of VASH1.

Original languageEnglish
Pages (from-to)3094-3101
Number of pages8
JournalJournal of cell science
Volume123
Issue number18
DOIs
Publication statusPublished - 2010 Sep 15

Keywords

  • Angiogenesis
  • Endothelial cell
  • Molecular chaperon
  • Secretion
  • Ubiquitylation
  • Vasohibin

ASJC Scopus subject areas

  • Cell Biology

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