Regulation of Insulin Receptor Trafficking by Bardet Biedl Syndrome Proteins. PLoS Genet 2015 Jun;11(6):e1005311
Date
06/24/2015Pubmed ID
26103456Pubmed Central ID
PMC4478011DOI
10.1371/journal.pgen.1005311Scopus ID
2-s2.0-84937800930 (requires institutional sign-in at Scopus site) 61 CitationsAbstract
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.
Author List
Starks RD, Beyer AM, Guo DF, Boland L, Zhang Q, Sheffield VC, Rahmouni KAuthor
Andreas M. Beyer PhD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsBardet-Biedl Syndrome
Cell Membrane
Cells, Cultured
Fibroblasts
HEK293 Cells
Humans
Insulin
Mice
Mice, Inbred C57BL
Microtubule-Associated Proteins
Mutation
Protein Binding
Protein Transport
Receptor, Insulin
