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    Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies

    Augustin, H. and McGourty, Kieran and Allen, M.J. and Madem, S.K. and Adcott, J. and Kerr, F. and Wong, C.T. and Vincent, A. and Godenschwege, T. and Boucrot, Emmanuel and Partridge, L. (2017) Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLOS Biology 15 (9), e2001655. ISSN 1545-7885.

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    Abstract

    Lowered insulin/insulin-like growth factor (IGF) signaling (IIS) can extend healthy lifespan in worms, flies, and mice, but it can also have adverse effects (the “insulin paradox”). Chronic, moderately lowered IIS rescues age-related decline in neurotransmission through the Drosophila giant fiber system (GFS), a simple escape response neuronal circuit, by increasing targeting of the gap junctional protein innexin shaking-B to gap junctions (GJs). Endosomal recycling of GJs was also stimulated in cultured human cells when IIS was reduced. Furthermore, increasing the activity of the recycling small guanosine triphosphatases (GTPases) Rab4 or Rab11 was sufficient to maintain GJs upon elevated IIS in cultured human cells and in flies, and to rescue age-related loss of GJs and of GFS function. Lowered IIS thus elevates endosomal recycling of GJs in neurons and other cell types, pointing to a cellular mechanism for therapeutic intervention into aging-related neuronal disorders.

    Metadata

    Item Type: Article
    School: Birkbeck Schools and Departments > School of Science > Biological Sciences
    Depositing User: Administrator
    Date Deposited: 13 Oct 2017 09:42
    Last Modified: 13 Oct 2017 09:42
    URI: http://eprints.bbk.ac.uk/id/eprint/20049

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