Journal article
Regulation of Insulin Receptor Trafficking by Bardet Biedl Syndrome Proteins
PLoS genetics, Vol.11(6), pp.e1005311-e1005311
06/2015
DOI: 10.1371/journal.pgen.1005311
PMCID: PMC4478011
PMID: 26103456
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.
Details
- Title: Subtitle
- Regulation of Insulin Receptor Trafficking by Bardet Biedl Syndrome Proteins
- Creators
- Rachel D Starks - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of AmericaAndreas M Beyer - Department of Internal Medicine, University of Iowa College of Medicine, Iowa City, Iowa, United States of AmericaDeng Fu Guo - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of AmericaLauren Boland - Department of Pharmacology, University of Iowa College of Medicine, Iowa City, Iowa, United States of AmericaQihong Zhang - 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 AmericaVal C Sheffield - 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 AmericaKamal Rahmouni - 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
- Resource Type
- Journal article
- Publication Details
- PLoS genetics, Vol.11(6), pp.e1005311-e1005311
- DOI
- 10.1371/journal.pgen.1005311
- PMID
- 26103456
- PMCID
- PMC4478011
- NLM abbreviation
- PLoS Genet
- ISSN
- 1553-7390
- eISSN
- 1553-7404
- Publisher
- Public Library Science; United States
- Grant note
- R01 EY011298 / NEI NIH HHS HL084207 / NHLBI NIH HHS EY-017168 / NEI NIH HHS Howard Hughes Medical Institute EY-011298 / NEI NIH HHS TL1 TR000443 / NCATS NIH HHS T32 GM007337 / NIGMS NIH HHS R01 EY017168 / NEI NIH HHS 1S10RR025439-01 / NCRR NIH HHS R01 NS083543 / NINDS NIH HHS P01 HL084207 / NHLBI NIH HHS S10 RR025439 / NCRR NIH HHS
- Language
- English
- Date published
- 06/2015
- Academic Unit
- Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Medical Genetics and Genomics; Neuroscience and Pharmacology; Internal Medicine; Ophthalmology and Visual Sciences
- Record Identifier
- 9984040018702771
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