Brain‐specific potential guanine nucleotide exchange factor for Arf, synArfGEF (Po), is localized to postsynaptic density

Journal of Neurochemistry - Tập 89 Số 6 - Trang 1347-1357 - 2004
Yuji Inaba1,2, Qing Bao Tian1, Akira Okano1, Jingping Zhang1, Hiroyuki Sakagami3, Shoko Miyazawa1, Weidong Li4,1, Atsushi Komiyama2, Kaoru Inokuchi5, Hisatake Kondo3, Tatsuo Suzuki1
1Department of Neuroplasticity, Research Institute on Aging and Adaptation
2Department of Pediatrics, Shinshu University Graduate School of Medicine, Matsumoto, Japan
3Division of Histology, Department of Cell Biology, Graduate School of Medicine, Tohoku University, Sendai, Miyagi, Japan
4Department of Neurobiology, Psychiatry, Psychology, Brain Research Institute, UCLA, Los Angeles, California, USA
5Mitsubishi Kagaku Institute of Life Sciences, Machida, Tokyo, Japan

Tóm tắt

AbstractWe cloned from a rat brain cDNA library a novel cDNA and named it a potential synaptic guanine nucleotide exchange factor (GEF) for Arf (synArfGEF (Po)) (GenBank Accession no. AB057643) based on its domain structure and localization. The cloned gene was 7410 bases long with a 3585‐bp coding sequence encoding a protein of 1194 amino acids. The deduced protein contained a coiled‐coil structure in the N‐terminal portion followed by Sec7 and Plekstrin homology (PH) domains. Thus, the protein was a member of the Sec7 family of proteins, GEFs. Conservation of the ADP‐ribosylation factor (Arf)‐binding sequence suggested that the protein was a GEF for Arf. The gene was expressed specifically in the brain, where it exhibited region‐specific expression. The protein was highly enriched in the postsynaptic density (PSD) fraction prepared from the rat forebrain. Uniquely, the protein interacted with PSD‐95, SAP97 and Homer/Vesl 1/PSD‐Zip45 via its C‐terminal PDZ‐binding motif and co‐localized with these proteins in cultured cortical neurons. These results supported its localization in the PSD. The postsynaptic localization was also supported by immunohistochemical examination of the rat brain. The mRNA for the synArfGEF was also localized to dendrites, as well as somas, of neuronal cells. Thus, both the mRNA and the protein were localized in the postsynaptic compartments. These results suggest a postsynaptic role of synArfGEF in the brain.

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