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

Hiroyuki Sakagami, Masashi Sanda, Masahiro Fukaya, Taisuke Miyazaki, Jun Sukegawa, Teruyuki Yanagisawa, Tatsuo Suzuki, Kohji Fukunaga, Masahiko Watanabe, Hisatake Kondo

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)199-212
Number of pages14
JournalNeuroscience Research
Volume60
Issue number2
DOIs
Publication statusPublished - 2008 Feb

Keywords

  • ADP-ribosylation factor
  • Guanine nucleotide exchange factor
  • Hippocampus
  • PSD-95
  • Postsynaptic density

ASJC Scopus subject areas

  • Neuroscience(all)

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