Glial Ca2+ signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability

  1. Shirley Weiss  Is a corresponding author
  2. Jan E Melom
  3. Kiel G Ormerod
  4. Yao V Zhang
  5. J Troy Littleton
  1. Massachusetts Institute of Technology, United States

Abstract

Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate neuronal function is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKXzydeco elevate basal Ca2+, predisposing animals to seizure-like behavior. To determine how cortex glial Ca2+ signaling controls neuronal excitability, we performed an in-vivo modifier screen of the NCKXzydeco seizure phenotype. We show that elevation of glial Ca2+ causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K2P channel, recapitulates NCKXzydeco seizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKXzydeco mutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca2+ signaling and the well-known role of glia in K+ buffering as a key mechanism for regulating neuronal excitability.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

Author details

  1. Shirley Weiss

    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States
    For correspondence
    s_weiss@MIT.EDU
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1006-349X
  2. Jan E Melom

    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kiel G Ormerod

    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Yao V Zhang

    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. J Troy Littleton

    The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5576-2887

Funding

National Institutes of Health (NS40296)

  • J Troy Littleton

National Institutes of Health (MH104536)

  • J Troy Littleton

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Graeme W Davis, University of California, San Francisco, United States

Publication history

  1. Received: December 6, 2018
  2. Accepted: April 25, 2019
  3. Accepted Manuscript published: April 26, 2019 (version 1)
  4. Version of Record published: May 10, 2019 (version 2)

Copyright

© 2019, Weiss et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Shirley Weiss
  2. Jan E Melom
  3. Kiel G Ormerod
  4. Yao V Zhang
  5. J Troy Littleton
(2019)
Glial Ca2+ signaling links endocytosis to K+ buffering around neuronal somas to regulate excitability
eLife 8:e44186.
https://doi.org/10.7554/eLife.44186

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