Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior
- Fred Hutchinson Cancer Research Center, United States
- Albert Einstein College of Medicine, United States
- University of Miami, United States
- 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.
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All data generated in this study are included in the manuscript and supporting files.
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Author details
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.
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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Glia actively sculpt sensory neurons by controlled phagocytosis to tune animal behavior
eLife 10:e63532.
https://doi.org/10.7554/eLife.63532
