Structural highlights
Function
RHOD_HUMAN Involved in endosome dynamics. May coordinate membrane transport with the function of the cytoskeleton. Involved in the internalization and trafficking of activated tyrosine kinase receptors such as PDGFRB. Participates in the reorganization of actin cytoskeleton; the function seems to involve WHAMM and includes regulation of filopodia formation and actin filament bundling. Can modulate the effect of DAPK3 in reorganization of actin cytoskeleton and focal adhesion dissolution.[1] [2] [3]
Publication Abstract from PubMed
Plexins are semaphorin receptors that play essential roles in mammalian neuronal axon guidance and in many other important mammalian biological processes. Plexin signaling depends on a semaphorin-induced dimerization mechanism and is modulated by small GTPases of the Rho family, of which RND1 serves as a plexin activator yet its close homolog RhoD an inhibitor. Using molecular dynamics (MD) simulations, we showed that RND1 reinforces the plexin dimerization interface, whereas RhoD destabilizes it due to their differential interaction with the cell membrane. Upon binding plexin at the Rho-GTPase-binding domain (RBD), RND1 and RhoD interact differently with the inner leaflet of the cell membrane and exert opposite effects on the dimerization interface via an allosteric network involving the RBD, RBD linkers, and a buttress segment adjacent to the dimerization interface. The differential membrane interaction is attributed to the fact that, unlike RND1, RhoD features a short C-terminal tail and a positively charged membrane interface.
A putative structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in mammalian plexin regulation.,Liu Y, Ke P, Kuo YC, Wang Y, Zhang X, Song C, Shan Y Elife. 2021 Jun 11;10:e64304. doi: 10.7554/eLife.64304. PMID:34114565[4]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Gad AK, Nehru V, Ruusala A, Aspenstrom P. RhoD regulates cytoskeletal dynamics via the actin nucleation-promoting factor WASp homologue associated with actin Golgi membranes and microtubules. Mol Biol Cell. 2012 Dec;23(24):4807-19. doi: 10.1091/mbc.E12-07-0555. Epub 2012, Oct 19. PMID:23087206 doi:http://dx.doi.org/10.1091/mbc.E12-07-0555
- ↑ Nehru V, Almeida FN, Aspenström P. Interaction of RhoD and ZIP kinase modulates actin filament assembly and focal adhesion dynamics. Biochem Biophys Res Commun. 2013 Apr 5;433(2):163-9. PMID:23454120 doi:10.1016/j.bbrc.2013.02.046
- ↑ Nehru V, Voytyuk O, Lennartsson J, Aspenström P. RhoD binds the Rab5 effector Rabankyrin-5 and has a role in trafficking of the platelet-derived growth factor receptor. Traffic. 2013 Dec;14(12):1242-54. PMID:24102721 doi:10.1111/tra.12121
- ↑ Liu Y, Ke P, Kuo YC, Wang Y, Zhang X, Song C, Shan Y. A putative structural mechanism underlying the antithetic effect of homologous RND1 and RhoD GTPases in mammalian plexin regulation. Elife. 2021 Jun 11;10:e64304. PMID:34114565 doi:10.7554/eLife.64304
