Glial Ca²⁺signaling links endocytosis to K⁺ buffering around neuronal somas to regulate excitability.

ABSTRACT: Glial-neuronal signaling at synapses is widely studied, but how glia interact with neuronal somas to regulate their activity is unclear. Drosophila cortex glia are restricted to brain regions devoid of synapses, providing an opportunity to characterize interactions with neuronal somas. Mutations in the cortex glial NCKX^zydeco elevate basal Ca²⁺, predisposing animals to seizure-like behavior. To determine how cortex glial Ca²⁺ signaling controls neuronal excitability, we performed an in vivo modifier screen of the NCKX^zydeco seizure phenotype. We show that elevation of glial Ca²⁺ causes hyperactivation of calcineurin-dependent endocytosis and accumulation of early endosomes. Knockdown of sandman, a K_2P channel, recapitulates NCKX^zydeco seizures. Indeed, sandman expression on cortex glial membranes is substantially reduced in NCKX^zydeco mutants, indicating enhanced internalization of sandman predisposes animals to seizures. These data provide an unexpected link between glial Ca²⁺ signaling and the well-known role of glia in K⁺ buffering as a key mechanism for regulating neuronal excitability.

SUBMITTER: Weiss S 

PROVIDER: S-EPMC6510531 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature