A Complete Survey of RhoGDI Targets Reveals Novel Interactions with Atypical Small GTPases

AHMAD MOKHTAR, Ana Masara binti, AHMED, Samrein, DARLING, Nicola J, HARRIS, Matthew, MOTT, Helen R and OWEN, Darerca (2021). A Complete Survey of RhoGDI Targets Reveals Novel Interactions with Atypical Small GTPases. Biochemistry, 60 (19), 1533-1551.

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Official URL: https://pubs.acs.org/doi/10.1021/acs.biochem.1c001...
Open Access URL: https://pubs.acs.org/doi/epdf/10.1021/acs.biochem.... (Published version)
Link to published version:: https://doi.org/10.1021/acs.biochem.1c00120

Abstract

There are three RhoGDIs in mammalian cells, which were initially defined as negative regulators of Rho family small GTPases. However, it is now accepted that RhoGDIs not only maintain small GTPases in their inactive GDP-bound form but also act as chaperones for small GTPases, targeting them to specific intracellular membranes and protecting them from degradation. Studies to date with RhoGDIs have usually focused on the interactions between the “typical” or “classical” small GTPases, such as the Rho, Rac, and Cdc42 subfamily members, and either the widely expressed RhoGDI-1 or the hematopoietic-specific RhoGDI-2. Less is known about the third member of the family, RhoGDI-3 and its interacting partners. RhoGDI-3 has a unique N-terminal extension and is found to localize in both the cytoplasm and the Golgi. RhoGDI-3 has been shown to target RhoB and RhoG to endomembranes. In order to facilitate a more thorough understanding of RhoGDI function, we undertook a systematic study to determine all possible Rho family small GTPases that interact with the RhoGDIs. RhoGDI-1 and RhoGDI-2 were found to have relatively restricted activity, mainly binding members of the Rho and Rac subfamilies. RhoGDI-3 displayed wider specificity, interacting with the members of Rho, Rac, and Cdc42 subfamilies but also forming complexes with “atypical” small Rho GTPases such as Wrch2/RhoV, Rnd2, Miro2, and RhoH. Levels of RhoA, RhoB, RhoC, Rac1, RhoH, and Wrch2/RhoV bound to GTP were found to decrease following coexpression with RhoGDI-3, confirming its role as a negative regulator of these small Rho GTPases.

Item Type: Article
Uncontrolled Keywords: 0304 Medicinal and Biomolecular Chemistry; 0601 Biochemistry and Cell Biology; 1101 Medical Biochemistry and Metabolomics; Biochemistry & Molecular Biology; 3101 Biochemistry and cell biology; 3205 Medical biochemistry and metabolomics; 3404 Medicinal and biomolecular chemistry
Identification Number: https://doi.org/10.1021/acs.biochem.1c00120
Page Range: 1533-1551
SWORD Depositor: Symplectic Elements
Depositing User: Symplectic Elements
Date Deposited: 25 Jan 2024 16:26
Last Modified: 25 Jan 2024 16:30
URI: https://shura.shu.ac.uk/id/eprint/33083

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