GABACReceptor Sensitivity Is Modulated by Interaction with MAP1B

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Abstract
GABACreceptors contain ρ subunits and mediate feedback inhibition from retinal amacrine cells to bipolar cells. We previously identified the cytoskeletal protein MAP1B as a ρ1 subunit anchoring protein. Here, we analyze the structural basis and functional significance of the MAP1B-ρ1 interaction. Twelve amino acids at the C terminus of the large intracellular loop of ρ1 (and also ρ2) are sufficient for interaction with MAP1B. Disruption of the MAP1B-ρ interaction in bipolar cells in retinal slices decreased the EC50of their GABACreceptors, doubling the receptors' current at low GABA concentrations without affecting their maximum current at high concentrations. Thus, anchoring to the cytoskeleton lowers the sensitivity of GABACreceptors and provides a likely site for functional modulation of GABACreceptor-mediated inhibition.