TY - JOUR
T1 - Cullin-3 and its adaptor protein ANKFY1 determine the surface level of integrin β1 in endothelial cells
AU - Maekawa, Masashi
AU - Tanigawa, Kazufumi
AU - Sakaue, Tomohisa
AU - Hiyoshi, Hiromi
AU - Kubota, Eiji
AU - Joh, Takashi
AU - Watanabe, Yuji
AU - Taguchi, Tomohiko
AU - Higashiyama, Shigeki
N1 - Funding Information:
Industrial Promotion Foundation (Research Grant for Industry from Academia 2016 to M.M.), Kanae Foundation for the Promotion of Medical Science (Grant for Research 2016 to M.M.), Novartis Pharmaceuticals Research (Grant 2017 to M.M.), Japan Agency for Medical Research and Development [Project for Cancer Research And Therapeutic Evolution (P-CREATE) and AMED 16cm0106219h0001 to S.H.].
Funding Information:
This work was supported by the Japan Society for the Promotion of Science (KAKENHI Grants JP16K19038 to M.M. and JP16H046980 to S.H.), Ehime
Publisher Copyright:
© 2017, Company of Biologists Ltd. All rights reserved.
PY - 2017/11/15
Y1 - 2017/11/15
N2 - Angiogenesis, the formation of new blood vessels from the preexisting 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.
AB - Angiogenesis, the formation of new blood vessels from the preexisting 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.
KW - Angiogenesis
KW - Cullin-3 (CUL3)
KW - Endothelial cells
KW - Integrin
KW - Membrane trafficking
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U2 - 10.1242/bio.029579
DO - 10.1242/bio.029579
M3 - Article
AN - SCOPUS:85034261169
SN - 2046-6390
VL - 6
SP - 1707
EP - 1719
JO - Biology Open
JF - Biology Open
IS - 11
ER -