Adhesion G protein-coupled receptor A2

Definition:

Endothelial receptor which functions together with RECK to enable brain endothelial cells to selectively respond to Wnt7 signals (WNT7A or WNT7B). Plays a key role in Wnt7-specific responses, such as endothelial cell sprouting and migration in the forebrain and neural tube, and establishment of the blood-brain barrier (By similarity). Acts as a Wnt7-specific coactivator of canonical Wnt signaling: required to deliver RECK-bound Wnt7 to frizzled by assembling a higher-order RECK-ADGRA2-Fzd-LRP5-LRP6 complex. ADGRA2-tethering function does not rely on its G-protein coupled receptor (GPCR) structure but instead on its combined capacity to interact with RECK extracellularly and recruit the Dishevelled scaffolding protein intracellularly. Binds to the glycosaminoglycans heparin, heparin sulfate, chondroitin sulfate and dermatan sulfate.

References:

[1]. Anshula Alok, et al. Wnt proteins synergize to activate β-catenin signaling. J Cell Sci. 2017 May 1;130(9):1532-1544. [Content Brief]

[2]. Marie Eubelen, et al. A molecular mechanism for Wnt ligand-specific signaling. Science. 2018 Aug 17;361(6403):eaat1178. [Content Brief]

[3]. Mario Vallon, et al. Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans. J Biol Chem. 2006 Nov 10;281(45):34179-88. [Content Brief]

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