PICK1 interacts with α7 neuronal nicotinic acetylcholine receptors and controls their clustering

Central to synaptic function are protein scaffolds associated with neurotransmitter receptors. α7 neuronal nicotinic acetylcholine receptors (nAChRs) modulate network activity, neuronal survival and cognitive processes in the CNS, but protein scaffolds that interact with these receptors are unknown. Here we show that the PDZ-domain containing protein PICK1 binds to α7 nAChRs and plays a role in their clustering. PICK1 interacted with the α7 cytoplasmic loop in yeast in a PDZ-dependent way, and the interaction was confirmed in recombinant pull-down experiments and by co-precipitation of native proteins. Some α7 and PICK1 clusters were adjacent at the surface of SH-SY5Y cells and GABAergic interneurons in hippocampal cultures. Expression of PICK1 caused decreased α7 clustering on the surface of the interneurons in a PDZ-dependent way. These data show that PICK1 negatively regulates surface clustering of α7 nAChRs on hippocampal interneurons, which may be important in inhibitory functions of α7 in the hippocampus.