The G protein-coupled receptor CL1 interacts directly with proteins of theShank family

PDZ domains play a pivotal role in the synaptic localization of ion channel s, receptors, signaling enzymes, and cell adhesion molecules. These domains mediate protein-protein interactions via the recognition of a conserved se quence motif at the extreme C terminus of their: target proteins. By means of a yeast two-hybrid screen using the C terminus of the G protein-coupled Lu-latrotoxin receptor CL1 as bait, three PDZ domain proteins of the Shank family were identified. These proteins belong to a single protein family ch aracterized by a common domain organization. The PDZ domain is highly conse rved among the family members, significantly different from other known PDZ domains, and specifically binds to the C terminus of CL1. Shank1 and CL1:a re expressed primarily in brain, and both proteins co-enrich in the postsyn aptic density. Furthermore, Shank1 induces a clustering of CL1 in transfect ed cells, strongly supporting an interaction of both proteins in vivo.