ZFIN ID: ZDB-PUB-130410-33
Essential Role of Sh3gl3 for Vascular Lumen Maintenance in Zebrafish
Zhao, Y., and Lin, S.
Date: 2013
Source: Arterioscler. Thromb. Vasc. Biol.   33(6): 1280-6 (Journal)
Registered Authors: Lin, Shuo
Keywords: Cbl-interacting protein of 85K, epidermal growth factor receptor, SH3-domain GRB2-like 3, vascular lumen zebrafish
MeSH Terms:
  • Adaptor Proteins, Signal Transducing/genetics
  • Adaptor Proteins, Signal Transducing/metabolism*
  • Animals
  • Aorta/metabolism*
  • GRB2 Adaptor Protein/genetics
  • GRB2 Adaptor Protein/metabolism*
  • Gene Expression Regulation
  • Models, Animal
  • Protein Binding
  • Sensitivity and Specificity
  • Signal Transduction/physiology
  • Vascular Patency/physiology*
  • Zebrafish
  • src Homology Domains/genetics*
PubMed: 23539215 Full text @ Arterioscler. Thromb. Vasc. Biol.

Objective—Studying the underlying molecular mechanisms for maintaining stereotyped vascular lumen diameters should help toward a comprehensive understanding of vascular homeostasis and function. We aimed to determine the role of SH3-domain GRB2-like 3 (Sh3gl3) and its interacting pathways in dorsal aorta (DA) maintenance in zebrafish.

Approach and Results—Sh3gl3 and its binding partner, Cbl-interacting protein of 85K (Cin85), together regulate endocytosis and were expressed in the developing vasculature. Morpholino (MO) knockdown of either gene resulted in shrinkage of the DA lumen, although artery/vein specification and the initial formation of vascular lumens were unaffected. In addition, sh3gl3 and cin85 MOs exerted a synergistic effect in causing the vascular phenotypes. To identify the signaling pathways in which Sh3gl3/Cin85 may participate, we screened several candidate inhibitors for their ability to induce similar circulatory defects. Chemical inhibition of the epidermal growth factor receptor and the phosphatidylinositol 3-kinase/Akt cascade led to a loss of circulation and shrunken DA in zebrafish embryos. Furthermore, inhibition of the epidermal growth factor receptor/phosphatidylinositol 3-kinase pathway showed a functional cooperation with Sh3gl3 deficiency in impairing DA lumens.

Conclusions—These results identify 2 new factors, Sh3gl3 and Cin85, which are essential for DA lumen maintenance, and suggest that endocytosis, possibly involving epidermal growth factor receptor and phosphatidylinositol 3-kinase, is implicated in Sh3gl3/Cin85 function.