RhoGDI3 and RhoG: Vesicular trafficking and interactions with the Sec3 Exocyst subunit.
Small GTPases. 2010-11-01; 1(3): 142-156
DOI: 10.4161/sgtp.1.3.15112
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1. Small GTPases. 2010 Nov;1(3):142-156.
RhoGDI3 and RhoG: Vesicular trafficking and interactions with the Sec3 Exocyst
subunit.
Morin A(1), Cordelières FP, Cherfils J, Olofsson B.
Author information:
(1)Laboratoire d’Enzymologie et Biochimie Structurales; Centre de Recherche de
Gif-sur-Yvette; CNRS; Gif-sur-Yvette, France.
RhoGDIs are negative regulators of small GTP-binding proteins of the Rho family,
which have essential cellular functions in most aspects of actin-based morphology
and motility processes. They extract Rho proteins from membranes, keep them in
inactive rhoGDI/Rho complexes and eventually deliver them again to specific
membranes in response to cellular signals. RhoGDI3, the most divergent member of
the rhoGDI family, is well suited to document the underlying molecular
mechanisms, since the active and inactive forms of its cellular target, RhoG,
have well-separated subcellular localizations. In this study, we investigate
trafficking structures and molecular interactions involved in rhoGDI3-mediated
shuttling of RhoG between the Golgi and the plasma membrane.Bimolecular
fluorescence complementation and acceptor-photobleaching FRET experiments suggest
that rhoGDI3 and RhoG form complexes on Golgi and vesicular structures in
mammalian cells. 4D-videomicroscopy confirms this localization, and show that
RhoG/rhoGDI3-labelled structures are less dynamic than RhoG and rhoGDI3-labeled
vesicles, consistent with the inhibitory function of rhoGDI3. Next, we identify
the Exocyst subunit Sec3 as a candidate rhoGDI3 partner in cells. RhoGDI3
relocates a subcomplex of the Exocyst (Sec3 and Sec8) from the cytoplasm to the
Golgi, while Sec6 is unaffected. Remarkably, Sec3 increases the level of
GTP-bound endogenous RhoG, the RhoG-dependent induction of membrane ruffles, and
the formation of intercellular tunneling nanotube-like protrusions.Altogether,
our study identifies a novel link between vesicular traffic and the regulation of
Rho proteins by rhoGDIs. It also suggests that components of the Exocyst
machinery may be involved in RhoG functions, possibly regulated by rhoGDI3.
DOI: 10.4161/sgtp.1.3.15112
PMCID: PMC3116606
PMID: 21686268