University Library
  • Login
A gateway to Melbourne's research publications
Minerva Access is the University's Institutional Repository. It aims to collect, preserve, and showcase the intellectual output of staff and students of the University of Melbourne for a global audience.
View Item 
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
  • Minerva Access
  • Medicine, Dentistry & Health Sciences
  • Florey Department of Neuroscience and Mental Health
  • Florey Department of Neuroscience and Mental Health - Research Publications
  • View Item
JavaScript is disabled for your browser. Some features of this site may not work without it.

    Drosophila Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity

    Thumbnail
    Download
    Published version (2.664Mb)

    Citations
    Scopus
    Web of Science
    Altmetric
    18
    15
    Author
    Post, S; Karashchuk, G; Wade, JD; Sajid, W; De Meyts, P; Tatar, M
    Date
    2018-05-28
    Source Title
    Frontiers in Endocrinology
    Publisher
    FRONTIERS MEDIA SA
    University of Melbourne Author/s
    Wade, John
    Affiliation
    Florey Department of Neuroscience and Mental Health
    Metadata
    Show full item record
    Document Type
    Journal Article
    Citations
    Post, S., Karashchuk, G., Wade, J. D., Sajid, W., De Meyts, P. & Tatar, M. (2018). Drosophila Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity. FRONTIERS IN ENDOCRINOLOGY, 9 (MAY), https://doi.org/10.3389/fendo.2018.00245.
    Access Status
    Open Access
    URI
    http://hdl.handle.net/11343/255174
    DOI
    10.3389/fendo.2018.00245
    Abstract
    Insulin and IGF signaling (IIS) is a complex system that controls diverse processes including growth, development, metabolism, stress responses, and aging. Drosophila melanogaster IIS is propagated by eight Drosophila insulin-like peptides (DILPs), homologs of both mammalian insulin and IGFs, with various spatiotemporal expression patterns and functions. DILPs 1-7 are thought to act through a single Drosophila insulin/IGF receptor, InR, but it is unclear how the DILPs thereby mediate a range of physiological phenotypes. We determined the distinct cell signaling effects of DILP2 and DILP5 stimulation upon Drosophila S2 cells. DILP2 and DILP5 induced similar transcriptional patterns but differed in signal transduction kinetics. DILP5 induced sustained phosphorylation of Akt, while DILP2 produced acute, transient Akt phosphorylation. Accordingly, we used phosphoproteomic analysis to identify distinct patterns of non-genomic signaling induced by DILP2 and DILP5. Across all treatments and replicates, 5,250 unique phosphopeptides were identified, representing 1,575 proteins. Among these peptides, DILP2, but not DILP5, dephosphorylated Ser15 on glycogen phosphorylase (GlyP), and DILP2, but not DILP5, was subsequently shown to repress enzymatic GlyP activity in S2 cells. The functional consequences of this difference were evaluated in adult Drosophila dilp mutants: dilp2 null adults have elevated GlyP enzymatic activity relative to wild type, while dilp5 mutants have reduced GlyP activity. In flies with intact insulin genes, GlyP overexpression extended lifespan in a Ser15 phosphorylation-dependent manner. In dilp2 mutants, that are otherwise long-lived, longevity was repressed by expression of phosphonull GlyP that is enzymatically inactive. Overall, DILP2, unlike DILP5, signals to affect longevity in part through its control of phosphorylation to deactivate glycogen phosphorylase, a central modulator of glycogen storage and gluconeogenesis.

    Export Reference in RIS Format     

    Endnote

    • Click on "Export Reference in RIS Format" and choose "open with... Endnote".

    Refworks

    • Click on "Export Reference in RIS Format". Login to Refworks, go to References => Import References


    Collections
    • Minerva Elements Records [45689]
    • Florey Department of Neuroscience and Mental Health - Research Publications [1052]
    Minerva AccessDepositing Your Work (for University of Melbourne Staff and Students)NewsFAQs

    BrowseCommunities & CollectionsBy Issue DateAuthorsTitlesSubjectsThis CollectionBy Issue DateAuthorsTitlesSubjects
    My AccountLoginRegister
    StatisticsMost Popular ItemsStatistics by CountryMost Popular Authors