title: Tamalin is a scaffold protein that interacts with multiple neuronal proteins in distinct modes of protein-protein association.
abstract: Tamalin is a scaffold protein that comprises multiple protein-interacting domains, including a 95-kDa postsynaptic density protein (PSD-95)/discs-large/ZO-1 (PDZ) domain, a leucine-zipper region, and a carboxyl-terminal PDZ binding motif. Tamalin forms a complex with metabotropic glutamate receptors and guanine nucleotide exchange factor cytohesins and promotes intracellular trafficking and cell surface expression of group 1 metabotropic glutamate receptors. In the present study, using several different approaches we have shown that tamalin interacts with multiple neuronal proteins through its distinct protein-binding domains. The PDZ domain of tamalin binds to the PDZ binding motifs of SAP90/PSD-95-associated protein and tamalin itself, whereas the PDZ binding motif of tamalin is capable of interacting with the PDZ domain of S-SCAM. In addition, tamalin forms a complex with PSD-95 and Mint2/X11beta/X11L by mechanisms different from the PDZ-mediated interaction. Tamalin has the ability to assemble with these proteins in vivo; their protein complex with tamalin was verified by coimmunoprecipitation of rat brain lysates. Interestingly, the distinct protein-interacting domains of tamalin are evolutionarily conserved, and mRNA expression is developmentally up-regulated at the postnatal period. The results indicate that tamalin exists as a key element that forms a protein complex with multiple postsynaptic and protein-trafficking scaffold proteins.
authors.affiliation: Department of Biological Sciences, Faculty of Medicine, and the Department of Molecular and System Biology, Graduate School of Biostudies, Kyoto University, Kyoto, 606-8501, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kitano
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Yamazaki
authors.forename: Kouji
authors.initials: K
authors.lastname: Kimura
authors.forename: Tomoko
authors.initials: T
authors.lastname: Masukado
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Nakajima
authors.forename: Shigetada
authors.initials: S
authors.lastname: Nakanishi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D015820:Cadherins; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism* / Q000502:physiology; D017124:Conserved Sequence; D000076122:Disks Large Homolog 4 Protein; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D009474:Neurons / Q000737:chemistry; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D051381:Rats; D000074407:SAP90-PSD95 Associated Proteins; D016415:Sequence Alignment
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C109650:Apba2 protein, rat; D015820:Cadherins; D002352:Carrier Proteins; C501444:DLG4 protein, human; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; C114103:Magi2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D000074407:SAP90-PSD95 Associated Proteins; C033652:postsynaptic density proteins; C410230:tamalin protein, human; D051528:Guanylate Kinases