Ananthalakshmy , Sundararaman and Harry, Mellor (2021) A functional antagonism between RhoJ and Cdc42 regulates fibronectin remodelling during angiogenesis. Small GTPases, 12 (4). pp. 241-245. ISSN 2154-1256

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Abstract

Angiogenesis is the formation of new blood vessels from pre-existing ones. Angiogenesis requires endothelial cells to change shape and polarity, as well as acquire the ability to directionally migrate ‒ processes that are classically regulated by the Rho family of GTPases. RhoJ (previously TCL) is an endothelium enriched Rho GTPase with a 78% amino acid similarity to the ubiquitously expressed Cdc42. In our recent publication, we demonstrate that α5β1 integrin co-traffics with RhoJ. RhoJ specifically represses the internalization of the active α5β1 conformer, leading to a reduced ability of endothelial cells to form fibronectin fibrils. Surprisingly, this function of RhoJ is in opposition to the role of Cdc42, a known driver of fibrillogenesis. Intriguingly, we discovered that the competition for limiting amounts of the shared effector, PAK3, could explain the ability of these two Rho GTPases to regulate fibrillogenesis in opposing directions. Consequently, RhoJ null mice show excessive fibronectin deposition around retinal vessels, possibly due to the unopposed action of Cdc42. Our work suggests that the functional antagonism between RhoJ and Cdc42 could restrict fibronectin remodelling to sites of active angiogenesis to form a provisional matrix for vessel growth. One correlate of our findings is that RhoJ dependent repression of fibronectin remodelling could be atheroprotective in quiescent vessels.

Item Type:	Article
Subjects:	Cardiovascular Diseases And Diabetes Biology
Depositing User:	Central Library RGCB
Date Deposited:	12 Jan 2022 09:32
Last Modified:	12 Jan 2022 09:32
URI:	http://rgcb.sciencecentral.in/id/eprint/1088

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