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

Augustin, Hrvoje ORCID: 0000-0002-2041-3844, McGourty, Kieran, Allen, Marcus J, Madem, Sirisha Kudumala, Adcott, Jennifer ORCID: 0000-0001-9146-3171, Kerr, Fiona ORCID: 0000-0003-3097-1951, Wong, Chi Tung, Vincent, Alec ORCID: 0000-0002-9201-2900, Godenschwege, Tanja, Boucrot, Emmanuel ORCID: 0000-0001-7312-6462
et al (show 1 more authors) (2017) Reduced insulin signaling maintains electrical transmission in a neural circuit in aging flies. PLoS biology, 15 (9). e2001655-.

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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.

Item Type: Article
Uncontrolled Keywords: Gap Junctions, Animals, Drosophila, Insulin, rab GTP-Binding Proteins, Somatomedins, Connexins, Escape Reaction, Synaptic Transmission, Aging, Female, Male
Depositing User: Symplectic Admin
Date Deposited: 04 Jun 2019 09:19
Last Modified: 17 Mar 2024 21:04
DOI: 10.1371/journal.pbio.2001655
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