title: Synaptic localization of membrane-associated guanylate kinase-interacting protein mediated by the pleckstrin homology domain.
abstract: Membrane-associated guanylate kinase-interacting protein (MAGUIN) has been identified as a protein binding postsynaptic density (PSD)-95 and synaptic scaffolding molecule (S-SCAM). MAGUIN has one sterile alpha motif, one conserved region in connector enhancer of ksr (Cnk) (CRIC), one PSD-95/Dlg-A/ZO-1 (PDZ) and one pleckstrin homology (PH) domain. There are two isoforms, MAGUIN-1 and -2. MAGUIN-1 binds the PDZ domains of PSD-95 and S-SCAM by the C-terminus, whereas MAGUIN-2 does not bind to PSD-95 or S-SCAM. Here, we have determined that MAGUIN-2 is also localized at synapses and that the synaptic localization of MAGUIN depends on the pleckstrin homology domain. The overexpressed C-terminal PDZ-binding region inhibits the synaptic targeting of PSD-95. Furthermore, the synaptic targeting of MAGUIN does not require N-methyl-d-aspartate (NMDA) receptor activity. These findings suggest that MAGUIN-1 and -2 are recruited to synapses by the PH domain and that MAGUIN-1 subsequently interacts with PSD-95 at synapses.
authors.affiliation: Department of Medical Biochemistry, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
authors.forename: Junko
authors.initials: J
authors.lastname: Iida
authors.forename: Wataru
authors.initials: W
authors.lastname: Nishimura
authors.forename: Ikuko
authors.initials: I
authors.lastname: Yao
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hata
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001798:Blood Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D006224:Cricetinae; D003712:Dendrites / Q000378:metabolism / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005260:Female; D005333:Fetus; D049452:Green Fluorescent Proteins; D006624:Hippocampus / Q000196:embryology* / Q000378:metabolism / Q000648:ultrastructure; D007202:Indicators and Reagents / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000378:metabolism; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism* / Q000648:ultrastructure; D010750:Phosphoproteins / Q000378:metabolism; D011247:Pregnancy; D017434:Protein Structure, Tertiary / Q000502:physiology; D051381:Rats; D017470:Receptors, Glutamate / Q000187:drug effects / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology*; D016708:Synaptophysin / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D001798:Blood Proteins; D002352:Carrier Proteins; C118898:Cnksr2 protein, rat; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D018691:Excitatory Amino Acid Antagonists; D007202:Indicators and Reagents; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D017470:Receptors, Glutamate; D016708:Synaptophysin; C039077:platelet protein P47; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins