Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior

  1. Stephan Raiders
  2. Erik Calvin Black
  3. Andrea Bae
  4. Stephen MacFarlane
  5. Mason Klein
  6. Shai Shaham
  7. Aakanksha Singhvi  Is a corresponding author
  1. Fred Hutchinson Cancer Research Center, United States
  2. Albert Einstein College of Medicine, United States
  3. University of Miami, United States
  4. The Rockefeller University, United States

Abstract

Glia in the central nervous system engulf neuron fragments to remodel synapses and recycle photoreceptor outer-segments. Whether glia passively clear shed neuronal debris, or actively prune neuron fragments is unknown. How pruning of single-neuron endings impacts animal behavior is also unclear. Here we report our discovery of glia-directed neuron pruning in C. elegans. Adult C. elegans AMsh glia engulf sensory endings of the AFD thermosensory neuron by repurposing components of the conserved apoptotic corpse phagocytosis machinery. The phosphatidylserine (PS) flippase TAT-1/ATP8A, functions with glial PS-receptor PSR-1/PSR and PAT-2/α-integrin to initiate engulfment. This activates glial CED-10/Rac1 GTPase through the ternary GEF complex of CED-2/CrkII, CED-5/DOCK180, CED-12/ELMO. Execution of phagocytosis uses the actin-remodeler WSP-1/nWASp. This process dynamically tracks AFD activity and is regulated by temperature, the AFD sensory input. Importantly, glial CED-10 levels regulate engulfment rates downstream of neuron activity, and engulfment-defective mutants exhibit altered AFD-ending shape and thermosensory behavior. Our findings reveal a molecular pathway underlying glia-dependent engulfment in a peripheral sense-organ, and demonstrate that glia actively engulf neuron-fragments, with profound consequences on neuron shape and animal sensory behavior.

Data availability

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

Article and author information

Author details

  1. Stephan Raiders

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Erik Calvin Black

    Basic Sciences Divsiion, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Andrea Bae

    Department of Neuroscience, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Stephen MacFarlane

    Cellular Imaging Shared Resources, Fred Hutchinson Cancer Research Center, Seattle, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Mason Klein

    Physics, Biology, University of Miami, Coral Gables, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8211-077X
  6. Shai Shaham

    Laboratory of Developmental Genetics, The Rockefeller University, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3751-975X
  7. Aakanksha Singhvi

    Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, United States
    For correspondence
    asinghvi@fredhutch.org
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5782-8536

Funding

Simons Foundation Autism Research Initiative (New Investigator Award)

  • Aakanksha Singhvi

American Federation for Aging Research (New Investigator Award)

  • Aakanksha Singhvi

NIH Office of the Director (R35NS105094)

  • Shai Shaham

NIH Office of the Director (NS114222)

  • Aakanksha Singhvi

NIH Office of the Director (T32AG066574)

  • Stephan Raiders

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

Reviewing Editor

  1. Douglas Portman, University of Rochester, United States

Publication history

  1. Received: September 29, 2020
  2. Accepted: March 23, 2021
  3. Accepted Manuscript published: March 24, 2021 (version 1)
  4. Version of Record published: April 27, 2021 (version 2)

Copyright

© 2021, Raiders 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. Stephan Raiders
  2. Erik Calvin Black
  3. Andrea Bae
  4. Stephen MacFarlane
  5. Mason Klein
  6. Shai Shaham
  7. Aakanksha Singhvi
(2021)
Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior
eLife 10:e63532.
https://doi.org/10.7554/eLife.63532

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