Synapse class-selective functions for WWC proteins!
The WW and C domain-containing gene (Wwc1–3) expression has been implicated in several brain disorders.
The researchers show that WWC2 regulates GABAA receptor surface expression and inhibitory synaptic function in the hippocampus. Mice lacking WWC2 expression in excitatory forebrain neurons, the authors show that WWC2 suppresses γ-aminobutyric acid type-A receptor (GABAAR) incorporation into the plasma membrane and regulates HAP1 and GRIP1, which form a complex promoting GABAAR recycling to the membrane. Inhibitory synaptic transmission is increased in CA1 pyramidal cells lacking WWC2.
They also identify divergent synaptic functions for WWC2 compared to WWC1 (KIBRA), a regulator of AMPAR trafficking and excitatory synaptic plasticity.
Thus, the researchers demonstrate synapse class-selective functions for WWC proteins as regulators of ionotropic neurotransmitter receptors and provide insight into mechanisms regulating GABAAR membrane expression.
https://www.cell.com/cell-reports/fulltext/S2211-1247(24)01192-6
