TMEM132B, a transmembrane protein, functions as a GABAA receptor (GABAAR) auxiliary subunit. It promotes GABAAR expression at the cell surface, slows receptor deactivation, and enhances alcohol's allosteric effects on the receptor. The TMEM132B-GABAAR complex is involved in GABAergic transmission pathways, and its function is crucial for understanding alcohol-related behaviors [1].

In TMEM132B knockout (KO) or TMEM132B I499A knockin (KI) mice where the TMEM132B-GABAAR interaction is abolished, GABAergic transmission in hippocampal neurons is decreased. Alcohol-induced potentiation of GABAAR-mediated currents is also diminished. Behaviorally, the anxiolytic and sedative/hypnotic effects of alcohol are reduced, while compulsive, binge-like alcohol consumption is increased. These findings from KO and KI mouse models reveal that TMEM132B is key in mediating alcohol-related behaviors in the brain [1].

In conclusion, TMEM132B plays a vital role in regulating GABAergic transmission and alcohol-related behaviors as demonstrated by mouse model-based research. Understanding TMEM132B function through these models provides insights into the molecular mechanisms of alcohol-related behaviors, potentially offering new strategies for addressing alcohol-related disorders.

References:

1. Wang, Guohao, Peng, Shixiao, Reyes Mendez, Miriam, Li, Yan, Lu, Wei. 2024. The TMEM132B-GABAA receptor complex controls alcohol actions in the brain. In Cell, 187, 6649-6668.e35. doi:10.1016/j.cell.2024.09.006. https://pubmed.ncbi.nlm.nih.gov/39357522/