title: The G protein-coupled receptor CL1 interacts directly with proteins of the Shank family.
abstract: PDZ domains play a pivotal role in the synaptic localization of ion channels, receptors, signaling enzymes, and cell adhesion molecules. These domains mediate protein-protein interactions via the recognition of a conserved sequence 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 alpha-latrotoxin receptor CL1 as bait, three PDZ domain proteins of the Shank family were identified. These proteins belong to a single protein family characterized by a common domain organization. The PDZ domain is highly conserved among the family members, significantly different from other known PDZ domains, and specifically binds to the C terminus of CL1. Shank1 and CL1 are expressed primarily in brain, and both proteins co-enrich in the postsynaptic density. Furthermore, Shank1 induces a clustering of CL1 in transfected cells, strongly supporting an interaction of both proteins in vivo.
authors.affiliation: Max Planck-Institute for Experimental Medicine, 37075 Göttingen, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Tobaben
authors.forename: T C
authors.initials: TC
authors.lastname: Südhof
authors.forename: B
authors.initials: B
authors.lastname: Stahl
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D020962:Heterotrimeric GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018000:Receptors, Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins; D016415:Sequence Alignment; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018000:Receptors, Peptide; D011993:Recombinant Fusion Proteins; C122162:SHANK2 protein, human; C492357:SHANK3 protein, human; C120531:Shank1 protein, rat; C485686:Shank2 protein, rat; C120532:Shank3 protein, rat; C034800:alpha-latrotoxin receptor; D020962:Heterotrimeric GTP-Binding Proteins