RIC-3 phosphorylation enables dual regulation of excitation and inhibition of Caenorhabditis elegans muscle

Gracia Safdie, Jana F. Liewald, Sarah Kagan, Emil Battat, Alexander Gottschalk, Millet Treinin*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

8 Scopus citations

Abstract

Brain function depends on a delicate balance between excitation and inhibition. Similarly, Caenorhabditis elegans motor system function depends on a precise balance between excitation and inhibition, as C. elegans muscles receive both inhibitory, GABAergic and excitatory, cholinergic inputs from motor neurons. Here we show that phosphorylation of the ER-resident chaperone of nicotinic acetylcholine receptors, RIC-3, leads to increased muscle excitability. RIC-3 phosphorylation at Ser-164 depends on opposing functions of the phosphatase calcineurin (TAX-6), and of the casein kinase II homologue KIN-10. Effects of calcineurin down-regulation and of phosphorylated RIC-3 on muscle excitability are mediated by GABAA receptor inhibition. Thus RIC-3 phosphorylation enables effects of this chaperone on GABAA receptors in addition to nAChRs. This dual effect provides coordinated regulation of excitation and inhibition and enables fine-Tuning of the excitation-inhibition balance. Moreover, regulation of inhibitory GABAA signaling by calcineurin, a calcium-And calmodulin-dependent phosphatase, enables homeostatic balancing of excitation and inhibition.

Original languageAmerican English
Pages (from-to)2994-3003
Number of pages10
JournalMolecular Biology of the Cell
Volume27
Issue number19
DOIs
StatePublished - 1 Oct 2016

Bibliographical note

Funding Information:
We thank Jean-Louis Bessereau for the UNC-63::YFP strain, Bruce Bamber for unc-49B and C clones, and the Caenorhabditis Genetics Center (St. Paul, MN) for strains. This work was funded by Israel Science Foundation Grants 352/10 and 388/15 and Deutsche Forsc-hungsgemeinschaft Grant EXC115 (Cluster of Excellence Frankfurt).

Publisher Copyright:
© 2016 Safdie et al.

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