A neuron type-specific microexon in <i>Ank3</i>/ankyrin-G modulates calcium activity and neuronal excitability.

ABSTRACT: Recent studies have revealed many alternative exons differentially spliced across diverse neuron types in the mammalian brain, but their links to neuronal physiology remain unclear. Here we characterize a deeply conserved microexon E35a in Ank3 encoding ankyrin-G (AnkG), a multifaceted adaptor protein best known as a master organizer of the axon initial segment (AIS) and as a leading genetic risk factor for bipolar disorder. E35a is predominantly skipped in cortical glutamatergic neurons but included in cortical GABAergic neurons and cerebellar neurons, which is dictated by multiple neuronal splicing factors. In E35a-deletion mice we generated, interneurons show increased excitability and somatic Ca²⁺ activity, without disruption in AIS. Biochemical analyses suggest that

SUBMITTER: Alam S 

PROVIDER: S-EPMC12713133 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature