An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans
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 peptid...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-02-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/49917 |
| _version_ | 1811180726988570624 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Bryan A Martinez |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T09:07:05Z |
| format | Article |
| id | doaj.art-57fd75f9b98c4541afadf21fad2aae7d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T09:07:05Z |
| publishDate | 2020-02-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-57fd75f9b98c4541afadf21fad2aae7d2022-12-22T04:32:35ZengeLife Sciences Publications LtdeLife2050-084X2020-02-01910.7554/eLife.49917An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegansBryan A Martinez0Pedro Reis Rodrigues1Ricardo M Nuñez Medina2Prosenjit Mondal3Neale J Harrison4https://orcid.org/0000-0001-6821-4089Museer A Lone5Amanda Webster6Aditi U Gurkar7Brock Grill8https://orcid.org/0000-0002-0379-3267Matthew S Gill9https://orcid.org/0000-0003-0818-8792Department of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Neuroscience, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesDepartment of Molecular Medicine, The Scripps Research Institute – Scripps Florida, Jupiter, United StatesIn 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.https://elifesciences.org/articles/49917dauer formationalternative splicinginsulin sensitivityDAF-2aging |
| spellingShingle | 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 An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans eLife dauer formation alternative splicing insulin sensitivity DAF-2 aging |
| title | An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans |
| title_full | An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans |
| title_fullStr | An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans |
| title_full_unstemmed | An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans |
| title_short | An alternatively spliced, non-signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in C. elegans |
| title_sort | alternatively spliced non signaling insulin receptor modulates insulin sensitivity via insulin peptide sequestration in c elegans |
| topic | dauer formation alternative splicing insulin sensitivity DAF-2 aging |
| url | https://elifesciences.org/articles/49917 |
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