Bipolar and schizophrenia risk gene AKAP11 encodes an autophagy receptor coupling the regulation of PKA kinase network homeostasis to synaptic transmission.

ABSTRACT: Human genomic studies have identified protein-truncating variants in AKAP11 associated with both bipolar disorder (BD) and schizophrenia (SCZ), implicating a shared disease mechanism driven by loss-of-function. AKAP11, a protein kinase A (PKA) adapter, plays a key role in degrading the PKA-RI complex through selective autophagy. However, the neuronal functions of AKAP11 and the impact of its loss-of-function remains largely uncharacterized. Through multi-omics approaches, cell biology, and electrophysiology analysis in mouse models and human induced neurons, we delineate a central role of AKAP11 in coupling PKA kinase network regulation to synaptic transmission. Loss of AKAP11 distorts compartment-specific PKA and GSΚ3α/β activities and impairs cellular functions that significantly overlap

SUBMITTER: Lee YK 

PROVIDER: S-EPMC12663438 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature