title: The postsynaptic density protein, IQ-ArfGEF/BRAG1, can interact with IRSp53 through its proline-rich sequence.
abstract: IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor for Arf1 and Arf6, is localized at the postsynaptic density (PSD) and interacts with PSD-95. In this study, we identified a novel interaction of IQ-ArfGEF/BRAG1 with insulin receptor tyrosine kinase substrate of 53 kDa (IRSp53), also known as brain-specific angiogenesis inhibitor 1-associated protein 2. The interaction was mediated by the binding of the C-terminal proline-rich sequence of IQ-ArfGEF/BRAG1 to the SH3 domain of IRSp53. IQ-ArfGEF/BRAG1 and IRSp53 were colocalized at the PSD of excitatory synapses of certain neuronal populations. Our present findings suggest that IQ-ArfGEF/BRAG1 may play roles downstream of NMDA receptors through the interaction with multivalent PSD proteins such as IRSp53 and PSD-95.
authors.affiliation: Department of Anatomy, Kitasato University School of Medicine, 1-15-1 Kitasato, Sagamihara, Kanagawa 228-8555, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Sanda
authors.forename: Akifumi
authors.initials: A
authors.lastname: Kamata
authors.forename: Osamu
authors.initials: O
authors.lastname: Katsumata
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hisatake
authors.initials: H
authors.lastname: Kondo
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sakagami
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002478:Cells, Cultured; D049229:Dendritic Spines / Q000378:metabolism / Q000648:ultrastructure; D000076122:Disks Large Homolog 4 Protein; D020662:Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D055232:Proline-Rich Protein Domains / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017434:Protein Structure, Tertiary / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D013570:Synaptic Membranes / Q000378:metabolism* / Q000648:ultrastructure; D009435:Synaptic Transmission / Q000502:physiology; D018909:src Homology Domains / Q000502:physiology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C539986:Baiap2 protein, mouse; C503229:Baiap2 protein, rat; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D020662:Guanine Nucleotide Exchange Factors; C539984:IQSEC2 protein, mouse; D047908:Intracellular Signaling Peptides and Proteins; C516347:Iqsec2 protein, rat; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D016194:Receptors, N-Methyl-D-Aspartate; C033652:postsynaptic density proteins; D051528:Guanylate Kinases