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Rho GTPases in Retinal Vascular Diseases

by 1,2,3,4,* and 5,6
Department of Ophthalmology and Visual Science, Nagoya City University Graduate School of Medical Sciences, Nagoya 467-8601, Japan
Department of Cell Biology, National Cerebral and Cardiovascular Center Research Institute, Osaka 564-8565, Japan
Proteo-Science Center, Ehime University, Toon 791-0295, Japan
Uemura Eye Clinic, Nishinomiya 663-8101, Japan
Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka 563-0871, Japan
Integrated Frontier Research for Medical Science Division, Institute for Open and Transdisciplinary Research Initiatives, Osaka University, Osaka 565-0871, Japan
Author to whom correspondence should be addressed.
Academic Editor: Ernestina Marianna De Francesco
Int. J. Mol. Sci. 2021, 22(7), 3684;
Received: 17 March 2021 / Revised: 30 March 2021 / Accepted: 31 March 2021 / Published: 1 April 2021
The Rho family of small GTPases (Rho GTPases) act as molecular switches that transduce extrinsic stimuli into cytoskeletal rearrangements. In vascular endothelial cells (ECs), Cdc42, Rac1, and RhoA control cell migration and cell–cell junctions downstream of angiogenic and inflammatory cytokines, thereby regulating vascular formation and permeability. While these Rho GTPases are broadly expressed in various types of cells, RhoJ is enriched in angiogenic ECs. Semaphorin 3E (Sema3E) releases RhoJ from the intracellular domain of PlexinD1, by which RhoJ induces actin depolymerization through competition with Cdc42 for their common effector proteins. RhoJ further mediates the Sema3E-induced association of PlexinD1 with vascular endothelial growth factor receptor (VEGFR) 2 and the activation of p38. Upon stimulation with VEGF-A, RhoJ facilitates the formation of a holoreceptor complex comprising VEGFR2, PlexinD1, and neuropilin-1, leading to the prevention of VEGFR2 degradation and the maintenance of intracellular signal transduction. These pleiotropic roles of RhoJ are required for directional EC migration in retinal angiogenesis. This review highlights the latest insights regarding Rho GTPases in the field of vascular biology, as it will be informative to consider their potential as targets for the treatment of aberrant angiogenesis and hyperpermeability in retinal vascular diseases. View Full-Text
Keywords: angiogenesis; cell–cell junction; cell migration; endothelial cell; retina; Rho GTPase; RhoJ; semaphorin 3E; vascular endothelial growth factor A; vascular permeability angiogenesis; cell–cell junction; cell migration; endothelial cell; retina; Rho GTPase; RhoJ; semaphorin 3E; vascular endothelial growth factor A; vascular permeability
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MDPI and ACS Style

Uemura, A.; Fukushima, Y. Rho GTPases in Retinal Vascular Diseases. Int. J. Mol. Sci. 2021, 22, 3684.

AMA Style

Uemura A, Fukushima Y. Rho GTPases in Retinal Vascular Diseases. International Journal of Molecular Sciences. 2021; 22(7):3684.

Chicago/Turabian Style

Uemura, Akiyoshi, and Yoko Fukushima. 2021. "Rho GTPases in Retinal Vascular Diseases" International Journal of Molecular Sciences 22, no. 7: 3684.

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