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miR-137 regulates PTP61F, affecting insulin signaling, metabolic homeostasis, and starvation resistance in Drosophila melanogaster

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dc.contributor.authorSaedi, Hana Ibrahim, author
dc.contributor.authorTsunoda, Susan, advisor
dc.contributor.authorHoerndli, Frederic, committee member
dc.contributor.authorAmberg, Gregory, committee member
dc.contributor.authorDi Pietro, Santiago, committee member
dc.date.accessioned2023-08-28T10:29:13Z
dc.date.available2025-08-28T10:27:54Z
dc.date.issued2023
dc.description.abstractmiR-137 is a highly conserved brain-enriched microRNA (miRNA) that has been associated with neuronal function and proliferation. Here, we show that Drosophila miR-137 null mutants display increased body weight with enhanced triglyceride and glucose levels and decreased locomotor activity. When challenged by nutrient deprivation, miR-137 mutants exhibit reduced motivation to feed and significantly prolonged survival. Together, these phenotypes suggest a new role for miR-137 in energy homeostasis. Genetic epistasis experiments show that the starvation resistance of miR-137 mutants involves the insulin signaling pathway, and that loss of miR-137 results in drastically reduced phosphorylation/activation of the single insulin receptor, InR, in Drosophila. We explore the possibility that the protein tyrosine phosphatase61F (PTP61F), ortholog of TC-PTP/PTP1B, known to dephosphorylate InR across species, is a potential in vivo target of miR-137. We show that loss of miR-137 results in upregulation of an endogenously tagged PTP61F protein, and that genetically increasing levels of PTP61F mimics the loss of phosphorylated InR and increased starvation resistance seen in miR-137 mutants. Finally, we show that the enhanced starvation resistance of miR-137 mutants is normalized by activation of the insulin signaling pathway in the nervous system. Our study introduces miR-137 as a new player in the regulation of central insulin signaling and metabolic homeostasis.
dc.format.mediumborn digital
dc.format.mediumdoctoral dissertations
dc.identifierSaedi_colostate_0053A_17812.pdf
dc.identifier.urihttps://hdl.handle.net/10217/237005
dc.languageEnglish
dc.language.isoeng
dc.publisherColorado State University. Libraries
dc.relation.ispartof2020-
dc.rightsCopyright and other restrictions may apply. User is responsible for compliance with all applicable laws. For information about copyright law, please see https://libguides.colostate.edu/copyright.
dc.rights.accessEmbargo expires: 08/28/2025.
dc.subjectinsulin signaling
dc.subjectmiR-137
dc.subjectstarvation resistance
dc.subjectmetabolic homeostasis
dc.subjectDrosophila melanogaster
dc.subjectPTP61F
dc.titlemiR-137 regulates PTP61F, affecting insulin signaling, metabolic homeostasis, and starvation resistance in Drosophila melanogaster
dc.typeText
dcterms.embargo.expires2025-08-28
dcterms.embargo.terms2025-08-28
dcterms.rights.dplaThis Item is protected by copyright and/or related rights (https://rightsstatements.org/vocab/InC/1.0/). You are free to use this Item in any way that is permitted by the copyright and related rights legislation that applies to your use. For other uses you need to obtain permission from the rights-holder(s).
thesis.degree.disciplineBiomedical Sciences
thesis.degree.grantorColorado State University
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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