rhoGDIs (Rho GDP dissociation inhibitors) are postulated to regulate the activity and the localization of small G-proteins of the Rho family by a shuttling process involving extraction of Rho from donor membranes, formation of inhibitory cytosolic rhoGDI/Rho complexes, and delivery of Rho to target membranes. However, the role of rhoGDIs in site-specific membrane targeting or extraction of Rho is still poorly understood. We investigated here the in vivo functions of two mammalian rhoGDIs: the specific rhoGDI-3 and the well-studied rhoGDI-1 (rhoGDI) after structure-based mutagenesis. We identified two sites in rhoGDIs, forming conserved interactions with their Rho target, whose mutation results in the uncoupling of inhibitory and shuttling functions of rhoGDIs in vivo. Remarkably, these rhoGDI mutants were detected at Rho-induced membrane ruffles or protrusions, where they co-localized with RhoG or Cdc42, probably identifying for the first time the site of extraction of a Rho protein by a rhoGDI in vivo. We propose that these mutations act by modifying the steady-state kinetics of the shuttling process regulated by rhoGDIs, such that transient steps at the cell membranes now become detectable. They should provide valuable tools for future investigations of the dynamics of membrane extraction or delivery of Rho proteins and their regulation by cellular partners.
Skip Nav Destination
Article navigation
August 2005
-
Cover Image
Cover Image
- PDF Icon PDF LinkFront Matter
- PDF Icon PDF LinkTable of Contents
Conference Article|
August 01 2005
RhoGDI-3, a promising system to investigate the regulatory function of rhoGDIs: uncoupling of inhibitory and shuttling functions of rhoGDIs
E. Dransart;
E. Dransart
1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR 9063, F-91198 Gif-sur-Yvette, France
Search for other works by this author on:
A. Morin;
A. Morin
1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR 9063, F-91198 Gif-sur-Yvette, France
Search for other works by this author on:
J. Cherfils;
J. Cherfils
1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR 9063, F-91198 Gif-sur-Yvette, France
Search for other works by this author on:
B. Olofsson
B. Olofsson
1
1Laboratoire d'Enzymologie et Biochimie Structurales, CNRS UPR 9063, F-91198 Gif-sur-Yvette, France
1To whom correspondence should be addressed (email olofsson@lebs.cnrs-gif.fr).
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 03 2005
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2005 The Biochemical Society
2005
Biochem Soc Trans (2005) 33 (4): 623–626.
Article history
Received:
March 03 2005
Citation
E. Dransart, A. Morin, J. Cherfils, B. Olofsson; RhoGDI-3, a promising system to investigate the regulatory function of rhoGDIs: uncoupling of inhibitory and shuttling functions of rhoGDIs. Biochem Soc Trans 1 August 2005; 33 (4): 623–626. doi: https://doi.org/10.1042/BST0330623
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Captcha Validation Error. Please try again.