Subcellular localization of coagulation factor II receptor-like 1 in neurons governs angiogenesis - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Nature Medicine Année : 2014

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

Christelle Boileau
  • Fonction : Auteur
  • PersonId : 758138
  • IdRef : 070286981

Résumé

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.
Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée
Loading...

Dates et versions

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

Identifiants

Citer

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
38 Consultations
3 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More