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: Rachel D Starks, Andreas M Beyer, Deng Fu Guo, Lauren Boland, Qihong Zhang, Val C Sheffield, Kamal Rahmouni
• Journal: PLoS genetics (PLoS Genet) Vol. 11 Issue 6 Pg. e1005311 (Jun 2015) ISSN: 1553-7404 [Electronic] United States
• PMID: 26103456 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Bbs1 protein, human
• Bbs1 protein, mouse
• Insulin
• Microtubule-Associated Proteins
• Receptor, Insulin

Topics

• Animals
• Bardet-Biedl Syndrome (genetics, metabolism)
• Cell Membrane (genetics, metabolism)
• Cells, Cultured
• Fibroblasts (metabolism)
• HEK293 Cells
• Humans
• Insulin (metabolism)
• Mice
• Mice, Inbred C57BL
• Microtubule-Associated Proteins (genetics, metabolism)
• Mutation
• Protein Binding
• Protein Transport
• Receptor, Insulin (metabolism)