Neuron cilia constrain glial regulators to microdomains around distal neurons
This article has been Reviewed by the following groups
Listed in
- Evaluated articles (Arcadia Science)
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.
Article activity feed
-
While further work is needed to identify the molecular identity of this cue, our data hint that this may be independent of proximal extra-cellular vesicle release
Are there any mutants that phenocopy ok288 that may point to possible candidates in neuronal cells that cue localization of KCC-3?
-
Indeed, we note punctate staining in internal vesicular compartments, suggesting that lack of basolateral targeting motifs likely stall KCC-2 membrane targeting
Does this fall into the "other" category? And what alternative types of localization fall into "other"?
-
First, lack of basolateral-targeting motifs in KCC-3 N-terminal region allows it to be shuttled apically to GAB. Once there, ciliary NRE signals act with the C-terminal 915-997 AA sequence to restrict KCC-3 to a microdomain.
This is a very thorough and detailed study digging into the mechanism of KCC-3’s apical localization in microdomains on AMsh glia. Beautiful work! I'm curious if you’ve looked at versions of KCC proteins that completely lack the N or C terminal variable regions? Assuming they still fold properly and are inserted in the membrane (maybe a stretch), the localization of these KCC mutants might help support these domain’s roles in targeting KCC apically or basolaterally.
-
