期刊
BIOLOGY OPEN
卷 6, 期 11, 页码 1707-1719出版社
COMPANY BIOLOGISTS LTD
DOI: 10.1242/bio.029579
关键词
Cullin-3 (CUL3); Integrin; Membrane trafficking; Endothelial cells; Angiogenesis
类别
资金
- Japan Society for the Promotion of Science (KAKENHI) [JP16K19038, JP16H046980]
- Ehime Industrial Promotion Foundation (Research Grant for Industry from Academia)
- Kanae Foundation for the Promotion of Medical Science
- Novartis Pharmaceuticals Research
- Japan Agency for Medical Research and Development [Project for Cancer Research And Therapeutic Evolution (P-CREATE)]
- Japan Agency for Medical Research and Development [AMED] [16cm0106219h0001]
- Grants-in-Aid for Scientific Research [16K19038, 17K09357, 16H04698, 15K18858, 16K18421] Funding Source: KAKEN
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 beta 1, 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 beta 1 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 beta 1. Our results highlight the multiple roles of CUL3 in angiogenesis, which are mediated through distinct CUL3-adaptor proteins.
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