Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis - Archive ouverte HAL Access content directly
Journal Articles Nature Medicine Year : 2014

Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis

(1, 2, 3) , (2) , (1) , (3, 4) , (1, 3, 4) , (2, 3) , (3, 4) , (4) , (2, 3) , (1, 4) , (2, 3) , (2, 3) , (5) , (2, 3) , (1, 4) , (1, 4) , (2, 3) , (2, 3) , (6) , (4) , (4) , (7) , (8) , (2, 3) , (1) , (1, 3, 2)
1
2
3
4
5
6
7
8
Christelle Boileau
  • Function : Author
  • PersonId : 758138
  • IdRef : 070286981

Abstract

Neurons have an important role in retinal vascular development. Here we show that the G protein-coupled receptor (GPCR) coagulation factor II receptor-like 1 (F2rl1, previously known as Par2) is abundant in retinal ganglion cells and is associated with new blood vessel formation during retinal development and in ischemic retinopathy. After stimulation, F2rl1 in retinal ganglion cells translocates from the plasma membrane to the cell nucleus using a microtubule-dependent shuttle that requires sorting nexin 11 (Snx11). At the nucleus, F2rl1 facilitates recruitment of the transcription factor Sp1 to trigger Vegfa expression and, in turn, neovascularization. In contrast, classical plasma membrane activation of F2rl1 leads to the expression of distinct genes, including Ang1, that are involved in vessel maturation. Mutant versions of F2rl1 that prevent nuclear relocalization but not plasma membrane activation interfere with Vegfa but not Ang1 expression. Complementary angiogenic factors are therefore regulated by the subcellular localization of a receptor (F2rl1) that governs angiogenesis. These findings may have implications for the selectivity of drug actions based on the subcellular distribution of their targets.
Embargoed file
Embargoed file
Ne sera jamais visible
Loading...

Dates and versions

inserm-02983633 , version 1 (30-10-2020)

Identifiers

Cite

Jean-Sébastien Joyal, Satra Nim, Tang Zhu, Nicholas Sitaras, José Carlos Rivera, et al.. Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis. Nature Medicine, 2014, 20 (10), pp.1165-1173. ⟨10.1038/nm.3669⟩. ⟨inserm-02983633⟩

Collections

INSERM
31 View
2 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More