Cited by 83Neuroscience and Neuropharmacology ResearchCellular transport and secretionProtein Kinase Regulation and GTPase Signaling

IQ-ArfGEF/BRAG1 is a guanine nucleotide exchange factor for Arf6 that interacts with PSD-95 at postsynaptic density of excitatory synapses.

Sakagami, Hiroyuki, Sanda, Masashi, Fukaya, Masahiro, Miyazaki, Taisuke, Sukegawa, Jun, Yanagisawa, Teruyuki, Suzuki, Tatsuo, Fukunaga, Kohji +2 more·2008·Neuroscience Research

Abstract

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.

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Crossref · 10.1016/j.neures.2007.10.013

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  • Members of the ARF family of small GTPases and their regulators are important regulators of spine density and morphology.

    “Members of the ADP-ribosylation factor (ARF) family of small GTPases and their regulators have gained increasing attention as important regulators of spine density and morphology [27], [28], [29].”

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Authors
Sakagami, H., Sanda, M., Fukaya, M., Miyazaki, T., Sukegawa, J., Yanagisawa, T., Suzuki, T., Fukunaga, K., Watanabe, M., & Kondo, H.
Affiliations
  • Tohoku University (JP)
  • Hokkaido University (JP)
  • Shinshu University (JP)
Corresponding author
Sakagami, Hiroyuki
Venue
Neuroscience Research
Publisher
Elsevier BV
Published
2008-02
Volume
60
Issue
2
Pages
199-212
ISSN
0168-0102 (ISSN-L)
OpenAlex
W2054545874
Cited by
83
References
1
Citations by year
2026: 3 · 2025: 6 · 2024: 4 · 2023: 6 · 2022: 3 · 2021: 6 · 2020: 5 · 2019: 7 · 2018: 3 · 2017: 2 · 2016: 12 · 2015: 4 · 2014: 1 · 2013: 3 · 2012: 6
FWCI
1.38
Type
journal article
Language
en
Open access
closed
Locations
  • Neuroscience Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords
ARF6, guanine nucleotide exchange factor, PSD-95, postsynaptic density, excitatory synapses, NMDA receptor, dendritic spines, dendritic transport, hippocampal neurons, cerebellar granule cells, small GTPase activation, asymmetrical synapses, inhibitory synapses
MeSH terms
Disks Large Homolog 4 Protein, ADP-Ribosylation Factor 6, Animals, Brain, Chlorocebus aethiops, Cloning, Molecular, Guinea Pigs, Membrane Proteins, Mice, Inbred C57BL, Neurons, Rabbits, Receptors, GABA-A, Synapses, Transfection, Receptors, N-Methyl-D-Aspartate, Gene Expression Regulation, Developmental, COS Cells, Guanine Nucleotide Exchange Factors, ADP-Ribosylation Factors, Electrophoretic Mobility Shift Assay, Immunoprecipitation, Intracellular Signaling Peptides and Proteins, Mice, Guanylate Kinases

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