TY - JOUR
T1 - IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses
AU - Sakagami, Hiroyuki
AU - Sanda, Masashi
AU - Fukaya, Masahiro
AU - Miyazaki, Taisuke
AU - Sukegawa, Jun
AU - Yanagisawa, Teruyuki
AU - Suzuki, Tatsuo
AU - Fukunaga, Kohji
AU - Watanabe, Masahiko
AU - Kondo, Hisatake
N1 - Funding Information:
We greatly appreciate Dr. Hiroshi Takeshima (Kyoto University Graduate School of Pharmaceutical Sciences) for a mouse cDNA library, Dr. Kazuhisa Nakayama (Kyoto University Graduate School of Pharmaceutical Sciences) for the expression vectors for ARFs and GGA1-GAT-GST fusion protein, Dr. Jun-Ichi Miyazaki (Osaka University Graduate School of Medicine) for pCAGGS vector, and Dr. Sachiko Saino-Saito (Tohoku University Graduate School of Medicine) for her assistance of non-radioactive in situ hybridization. This work is supported by Grants-in-Aid for Scientific Research to HS (#19300119) and to HK (#18390056 and #18659049) from the Ministry of Education, Science, Sports, Culture and Technology of Japan.
PY - 2008/2
Y1 - 2008/2
N2 - ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates dendritic differentiation possibly through the organization of actin cytoskeleton and membrane traffic. Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1. IQ-ArfGEF/BRAG1 mRNA was abundantly expressed in the brain with higher levels in forebrain structures and cerebellar granule cells. In hippocampal neurons, IQ-ArfGEF/BRAG1 mRNA was localized not only at neuronal cell bodies but also at dendritic processes, indicating its dendritic transport and localization. Immunoprecipitation and in vitro binding experiments revealed that IQ-ArfGEF/BRAG1 formed a protein complex with N-methyl-d-aspartate (NMDA)-type glutamate receptors through the interaction with a postsynaptic density (PSD) scaffold protein, PSD-95. Immunohistochemical analysis demonstrated that IQ-ArfGEF/BRAG1 was localized preferentially at the postsynaptic density of asymmetrical synapses on dendritic spines, but was lacking at GABAa receptor-carrying inhibitory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.
AB - ADP ribosylation factor 6 (Arf6) is a small GTPase that regulates dendritic differentiation possibly through the organization of actin cytoskeleton and membrane traffic. Here, we characterized IQ-ArfGEF/BRAG1, a guanine nucleotide exchange factor (GEF) for Arf6, in the mouse brain. In vivo Arf pull down assay demonstrated that IQ-ArfGEF/BRAG1 activated Arf6 more potently than Arf1. IQ-ArfGEF/BRAG1 mRNA was abundantly expressed in the brain with higher levels in forebrain structures and cerebellar granule cells. In hippocampal neurons, IQ-ArfGEF/BRAG1 mRNA was localized not only at neuronal cell bodies but also at dendritic processes, indicating its dendritic transport and localization. Immunoprecipitation and in vitro binding experiments revealed that IQ-ArfGEF/BRAG1 formed a protein complex with N-methyl-d-aspartate (NMDA)-type glutamate receptors through the interaction with a postsynaptic density (PSD) scaffold protein, PSD-95. Immunohistochemical analysis demonstrated that IQ-ArfGEF/BRAG1 was localized preferentially at the postsynaptic density of asymmetrical synapses on dendritic spines, but was lacking at GABAa receptor-carrying inhibitory synapses. Taken together, IQ-ArfGEF/BRAG1 forms a postsynaptic protein complex containing PSD-95 and NMDA receptors at excitatory synapses, where it may function as a GEF for Arf6.
KW - ADP-ribosylation factor
KW - Guanine nucleotide exchange factor
KW - Hippocampus
KW - PSD-95
KW - Postsynaptic density
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U2 - 10.1016/j.neures.2007.10.013
DO - 10.1016/j.neures.2007.10.013
M3 - Article
C2 - 18164504
AN - SCOPUS:38649136943
VL - 60
SP - 199
EP - 212
JO - Neuroscience Research
JF - Neuroscience Research
SN - 0168-0102
IS - 2
ER -