FMRP regulates GABA_A receptor channel activity to control signal integration in hippocampal granule cells.

ABSTRACT: Fragile X syndrome, the most common inherited form of intellectual disability, is caused by loss of fragile X mental retardation protein (FMRP). GABAergic system dysfunction is one of the hallmarks of FXS, yet the underlying mechanisms remain poorly understood. Here, we report that FMRP interacts with GABA_A receptor (GABA_AR) and modulates its single-channel activity. Specifically, FMRP regulates spontaneous GABA_AR opening through modulating its single-channel conductance and open probability in dentate granule cells. FMRP loss reduces spontaneous GABA_AR activity underlying tonic inhibition, while N-terminal FMRP fragment (aa 1-297) is sufficient to rapidly normalize tonic inhibition in Fmr1 knockout (KO) granule cells. FMRP-GABA_AR inte

SUBMITTER: Deng PY 

PROVIDER: S-EPMC9175534 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature