LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes

Herdenberg, C. et al. (2021) LRIG proteins regulate lipid metabolism via BMP signaling and affect the risk of type 2 diabetes. Communications Biology, 4, 90. (doi: 10.1038/s42003-020-01613-w) (PMID:33469151) (PMCID:PMC7815736)

Abstract

Leucine-rich repeats and immunoglobulin-like domains (LRIG) proteins have been implicated as regulators of growth factor signaling; however, the possible redundancy among mammalian LRIG1, LRIG2, and LRIG3 has hindered detailed elucidation of their physiological functions. Here, we show that Lrig-null mouse embryonic fibroblasts (MEFs) are deficient in adipogenesis and bone morphogenetic protein (BMP) signaling. In contrast, transforming growth factor-beta (TGF-β) and receptor tyrosine kinase (RTK) signaling appeared unaltered in Lrig-null cells. The BMP signaling defect was rescued by ectopic expression of LRIG1 or LRIG3 but not by expression of LRIG2. Caenorhabditis elegans with mutant LRIG/sma-10 variants also exhibited a lipid storage defect. Human LRIG1 variants were strongly associated with increased body mass index (BMI) yet protected against type 2 diabetes; these effects were likely mediated by altered adipocyte morphology. These results demonstrate that LRIG proteins function as evolutionarily conserved regulators of lipid metabolism and BMP signaling and have implications for human disease.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Strawbridge, Dr Rona
• Authors: Herdenberg, C., Mutie, P. M., Billing, O., Abdullah, A., Strawbridge, R. J., Dahlman, I., Tuck, S., Holmlund, C., Arner, P., Henriksson, R., Franks, P. W., and Hedman, H.
• College/School: College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing
• Journal Name: Communications Biology
• Publisher: Nature Research
• ISSN: 2399-3642
• ISSN (Online): 2399-3642
• Copyright Holders: Copyright © The Author(s) 2021
• First Published: First published in Communications Biology 4:90
• Publisher Policy: Reproduced under a Creative Commons license

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
302131		Understanding the excess risk of cardiometabolic disease in individuals with serious mental illness	Jill Pell	Medical Research Council (MRC)	MR/S003061/1	HW - Public Health