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

Hrvoje Augustin, Kieran McGourty, Marcus J. Allen, Sirisha Kudumala Madem, Jennifer Adcot, Fiona Kerr, Chi Tung Wong, Alec Vincent, Tanja Godenschwege, Emmanuel Boucrot, Linda Partridge*

*Corresponding author for this work

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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.
Original languageEnglish
Article numbere2001655
Number of pages25
JournalPLoS Biology
Volume15
Issue number9
DOIs
Publication statusPublished - 13 Sep 2017

Keywords

  • insulin signalling
  • neuroscience
  • neuronal disorders

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    Augustin, H., McGourty, K., Allen, M. J., Madem, S. K., Adcot, J., Kerr, F., Wong, C. T., Vincent, A., Godenschwege, T., Boucrot, E., & Partridge, L. (2017). Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLoS Biology, 15(9), [e2001655]. https://doi.org/10.1371/journal.pbio.2001655