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- Title
The N-terminal coiled-coil domain of the cytohesin/ARNO family of guanine nucleotide exchange factors interacts with Gαq.
- Authors
Geneviève Laroche; Patrick Giguère; Ãmilie Dupré; Gilles Dupuis; Jean-Luc Parent
- Abstract
Abstract  Cytohesins are guanine-nucleotide exchange factors (GEF) for the Arf family of GTPases. One member of the Arf family, ARF6, plays an active role in the intracellular trafficking of G protein-coupled receptors. We have previously reported that Gαq signaling leads to the activation of ARF6, possibly through a direct interaction with cytohesin-2/ARNO. Here, we report that Gαq can directly interact with cytohesin-1, another Arf-GEF of the ARNO/cytohesin family. Cytohesin-1 preferentially associated with a constitutively active mutant of Gαq (Gαq-Q209L) compared to wild-type Gαq in HEK293 cells. Stimulation of TPβ, a Gαq-coupled receptor, to activate Gαq resulted in the promotion of a protein complex between Gαq and cytohesin-1. Confocal immunofluorescence microscopy revealed that wild-type Gαq and cytohesin-1 co-localized in intracellular compartments and at or near the plasma membrane. In contrast, expression of Gαq-Q209L induced a drastic increase in the localization of cytohesin-1 at the plasma membrane. Expression of a dominant-negative mutant of cytohesin-1 reduced by 40% the agonist-induced internalization of TPβ, a process that we previously demonstrated to be dependent on Gαq-mediated signaling and Arf6 activation. Using deletion mutants, we show that cytohesin-1 interacts with Gαq through its N-terminal coiled-coil domain. Cytohesin-1 and cytohesin-2/ARNO mutants lacking the coiled-coil domain were unable to relay Gαq-mediated activation of Arf6. This is the first report of an interaction between the coiled-coil domain of the cytohesin/ARNO family of Arf-GEFs and a member of the heterotrimeric G proteins.
- Subjects
MEMBRANE proteins; G proteins; CELL membranes; IMMUNOCYTOCHEMISTRY
- Publication
Molecular & Cellular Biochemistry, 2007, Vol 306, Issue 1/2, p141
- ISSN
0300-8177
- Publication type
Article
- DOI
10.1007/s11010-007-9564-9