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An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans

Authors :
Bryan A Martinez
Pedro Reis Rodrigues
Ricardo M Nuñez Medina
Prosenjit Mondal
Neale J Harrison
Museer A Lone
Amanda Webster
Aditi U Gurkar
Brock Grill
Matthew S Gill
Source :
eLife, Vol 9 (2020)
Publication Year :
2020
Publisher :
eLife Sciences Publications Ltd, 2020.

Abstract

In the nematode C. elegans, insulin signaling regulates development and aging in response to the secretion of numerous insulin peptides. Here, we describe a novel, non-signaling isoform of the nematode insulin receptor (IR), DAF-2B, that modulates insulin signaling by sequestration of insulin peptides. DAF-2B arises via alternative splicing and retains the extracellular ligand binding domain but lacks the intracellular signaling domain. A daf-2b splicing reporter revealed active regulation of this transcript through development, particularly in the dauer larva, a diapause stage associated with longevity. CRISPR knock-in of mScarlet into the daf-2b genomic locus confirmed that DAF-2B is expressed in vivo and is likely secreted. Genetic studies indicate that DAF-2B influences dauer entry, dauer recovery and adult lifespan by altering insulin sensitivity according to the prevailing insulin milieu. Thus, in C. elegans alternative splicing at the daf-2 locus generates a truncated IR that fine-tunes insulin signaling in response to the environment.

Details

Language :
English
ISSN :
2050084X
Volume :
9
Database :
Directory of Open Access Journals
Journal :
eLife
Publication Type :
Academic Journal
Accession number :
edsdoj.57fd75f9b98c4541afadf21fad2aae7d
Document Type :
article
Full Text :
https://doi.org/10.7554/eLife.49917