Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin β1 in endothelial cells

Biology Open

Kazufumi Tanigawa¹  Takashi Joh²  Eiji Kubota²  Hiromi Hiyoshi²  Yuji Watanabe³  Tomohiko Taguchi⁴  Shigeki Higashiyama⁵  Tomohisa Sakaue⁵  Masashi Maekawa⁵ 

[1] Department of Biochemistry and Molecular Genetics, Ehime University Graduate School of Medicine, Matsuyama 791-0295, Japan;Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya City 467-8601, Japan;Department of Gastrointestinal Surgery and Surgical Oncology, Ehime University Graduate School of Medicine, Matsuyama 791-0295, Japan;Department of Health Chemistry, Graduate School of Pharmaceutical Science, University of Tokyo, Tokyo 113-0033, Japan;Division of Cell Growth and Tumor Regulation, Proteo-Science Center, Ehime University, Matsuyama 791-0295, Japan;

关键词: Cullin-3 (CUL3);    Integrin;    Membrane trafficking;    Endothelial cells;    Angiogenesis;   

DOI  :  10.1242/bio.029579

来源: DOAJ

【 摘 要 】

Angiogenesis, the formation of new blood vessels from the pre-existing vasculature, is related to numerous pathophysiological events. We previously reported that a RING ubiquitin ligase complex scaffold protein, cullin-3 (CUL3), and one of its adaptor proteins, BAZF, regulated angiogenesis in the mouse retina by suppressing Notch signaling. However, the degree of inhibition of angiogenesis was made greater by CUL3 depletion than by BAZF depletion, suggesting other roles of CUL3 in angiogenesis besides the regulation of Notch signaling. In the present study, we found that CUL3 was critical for the cell surface level of integrin β1, an essential cell adhesion molecule for angiogenesis in HUVECs. By siRNA screening of 175 BTBPs, a family of adaptor proteins for CUL3, we found that ANKFY1/Rabankyrin-5, an early endosomal BTBP, was also critical for localization of surface integrin β1 and angiogenesis. CUL3 interacted with ANKFY1 and was required for the early endosomal localization of ANKFY1. These data suggest that CUL3/ANKFY1 regulates endosomal membrane traffic of integrin β1. Our results highlight the multiple roles of CUL3 in angiogenesis, which are mediated through distinct CUL3-adaptor proteins.

【 授权许可】

Unknown