title: Regulation of Insulin Receptor Trafficking by Bardet Biedl Syndrome Proteins.
abstract: Insulin and its receptor are critical for the regulation of metabolic functions, but the mechanisms underlying insulin receptor (IR) trafficking to the plasma membrane are not well understood. Here, we show that Bardet Biedl Syndrome (BBS) proteins are necessary for IR localization to the cell surface. We demonstrate that the IR interacts physically with BBS proteins, and reducing the expression of BBS proteins perturbs IR expression in the cell surface. We show the consequence of disrupting BBS proteins for whole body insulin action and glucose metabolism using mice lacking different BBS genes. These findings demonstrate the importance of BBS proteins in underlying IR cell surface expression. Our data identify defects in trafficking and localization of the IR as a novel mechanism accounting for the insulin resistance commonly associated with human BBS. This is supported by the reduced surface expression of the IR in fibroblasts derived from patients bearing the M390R mutation in the BBS1 gene.
authors.affiliation: Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Rachel D
authors.initials: RD
authors.lastname: Starks
authors.affiliation: Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Beyer
authors.affiliation: Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Deng Fu
authors.initials: DF
authors.lastname: Guo
authors.affiliation: Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Lauren
authors.initials: L
authors.lastname: Boland
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, United States of America; Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Qihong
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Pediatrics, University of Iowa College of Medicine, Iowa City, Iowa, United States of America; Howard Hughes Medical Institute, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Val C
authors.initials: VC
authors.lastname: Sheffield
authors.affiliation: Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of America; Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United States of America; FOE Diabetes Research Center, University of Iowa College of Medicine, Iowa City, Iowa, United States of America.
authors.forename: Kamal
authors.initials: K
authors.lastname: Rahmouni
mesh_terms: D000818:Animals; D020788:Bardet-Biedl Syndrome / Q000235:genetics* / Q000378:metabolism; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D005347:Fibroblasts / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D007328:Insulin / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D011485:Protein Binding; D021381:Protein Transport; D011972:Receptor, Insulin / Q000378:metabolism*
chemical_list: C464790:Bbs1 protein, human; C506280:Bbs1 protein, mouse; D007328:Insulin; D008869:Microtubule-Associated Proteins; D011972:Receptor, Insulin