Epilepsy gene prickle ensures neuropil glial ensheathment through regulating cell adhesion molecules.

ABSTRACT: Human PRICKLE1 gene has been associated with epilepsy. However, the underlying pathogenetic mechanisms remain elusive. Here we report a Drosophila prickle mutant pk ^IG1-1 exhibiting strong epileptic seizures and, intriguingly, abnormal glial wrapping. We found that pk is required in both neurons and glia, particularly neuropil ensheathing glia (EGN), the fly analog of oligodendrocyte, for protecting the animal from seizures. We further revealed that Pk directly binds to the membrane skeleton binding protein Ankyrin 2 (Ank2), thereby regulating the cell adhesion molecule Neuroglian (Nrg). Such protein interactions also apply to their human homologues. Moreover, nrg and ank2 mutant flies also display seizure phenotypes, and expression of e

SUBMITTER: Chen Y 

PROVIDER: S-EPMC9792895 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature