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Neuron cilia constrain glial regulators to microdomains around distal neurons

Sneha Ray, Pralaksha Gurung, R. Sean Manning, Alexandra Kravchuk, View ORCID ProfileAakanksha Singhvi
doi: https://doi.org/10.1101/2023.03.18.533255
Sneha Ray
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
2Neuroscience Graduate Program, University of Washington, Seattle, WA
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Pralaksha Gurung
2Neuroscience Graduate Program, University of Washington, Seattle, WA
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R. Sean Manning
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
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Alexandra Kravchuk
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
3University of Washington School of Medicine, WA 98195
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Aakanksha Singhvi
1Division of Basic Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109
4Department of Biological Structure, University of Washington School of Medicine, WA 98195
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  • ORCID record for Aakanksha Singhvi
  • For correspondence: asinghvi@fredhutch.org
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ABSTRACT

Each glia interacts with multiple neurons, but the fundamental logic of whether it interacts with all equally remains unclear. We find that a single sense-organ glia modulates different contacting neurons distinctly. To do so, it partitions regulatory cues into molecular microdomains at specific neuron contact-sites, at its delimited apical membrane. For one glial cue, K/Cl transporter KCC-3, microdomain-localization occurs through a two-step, neuron-dependent process. First, KCC-3 shuttles to glial apical membranes. Second, some contacting neuron cilia repel it, rendering it microdomain-localized around one distal neuron-ending. KCC-3 localization tracks animal aging, and while apical localization is sufficient for contacting neuron function, microdomain-restriction is required for distal neuron properties. Finally, we find the glia regulates its microdomains largely independently. Together, this uncovers that glia modulate cross-modal sensor processing by compartmentalizing regulatory cues into microdomains. Glia across species contact multiple neurons and localize disease-relevant cues like KCC-3. Thus, analogous compartmentalization may broadly drive how glia regulate information processing across neural circuits.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted March 19, 2023.
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Neuron cilia constrain glial regulators to microdomains around distal neurons
Sneha Ray, Pralaksha Gurung, R. Sean Manning, Alexandra Kravchuk, Aakanksha Singhvi
bioRxiv 2023.03.18.533255; doi: https://doi.org/10.1101/2023.03.18.533255
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Neuron cilia constrain glial regulators to microdomains around distal neurons
Sneha Ray, Pralaksha Gurung, R. Sean Manning, Alexandra Kravchuk, Aakanksha Singhvi
bioRxiv 2023.03.18.533255; doi: https://doi.org/10.1101/2023.03.18.533255

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