title: Scaffolding protein IQGAP1: an insulin-dependent link between caveolae and the cytoskeleton in primary human adipocytes?
abstract: The ubiquitously expressed IQ motif-containing GTPase activating protein-1 (IQGAP1) is a scaffolding protein implicated in an array of cellular functions, in particular by binding to cytoskeletal elements and signaling proteins. A role of IQGAP1 in adipocytes has not been reported. We therefore investigated the cellular IQGAP1 interactome in primary human adipocytes. Immunoprecipitation and quantitative mass spectrometry identified caveolae and caveolae-associated proteins as the major IQGAP1 interactors alongside cytoskeletal proteins. We confirmed co-localization of IQGAP1 with the defining caveolar marker protein caveolin-1 by confocal microscopy and proximity ligation assay. Most interestingly, insulin enhanced the number of IQGAP1 interactions with caveolin-1 by five-fold. Moreover, we found a significantly reduced abundance of IQGAP1 in adipocytes from patients with type 2 diabetes compared with cells from nondiabetic control subjects. Both the abundance of IQGAP1 protein and mRNA were reduced, indicating a transcriptional defect in diabetes. Our findings suggest a novel role of IQGAP1 in insulin-regulated interaction between caveolae and cytoskeletal elements of the adipocyte, and that this is quelled in the diabetic state.
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE58185 Linköping, Sweden.
authors.forename: Åsa
authors.initials: Å
authors.lastname: Jufvas
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE58185 Linköping, Sweden.
authors.forename: Meenu R
authors.initials: MR
authors.lastname: Rajan
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE58185 Linköping, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Jönsson
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE58185 Linköping, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Strålfors
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, SE58185 Linköping, Sweden.
authors.forename: Maria V
authors.initials: MV
authors.lastname: Turkina
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D021941:Caveolae / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D010766:Phosphorylation; D020703:ras GTPase-Activating Proteins / Q000378:metabolism*
chemical_list: C101203:IQ motif containing GTPase activating protein 1; D007328:Insulin; D020703:ras GTPase-Activating Proteins
keywords: IQGAP1; adipocyte; caveolae; caveolin-1; cytoskeletal proteins