QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Kubo, T. Articles by Tohyama, M. Search for Related Content PubMed PubMed Citation Articles by Kubo, T. Articles by Tohyama, M.

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 1, 2002, 22(19):8504-8513

A Novel FERM Domain Including Guanine Nucleotide Exchange Factor Is Involved in Rac Signaling and Regulates Neurite Remodeling

Tateki Kubo^{1, 2, 3}, Toshihide Yamashita^{1, 3}, Atsushi Yamaguchi^{1, 3}, Hideki Sumimoto⁴, Ko Hosokawa², and Masaya Tohyama^{1, 3}

Departments of ¹ Anatomy and Neuroscience and ² Plastic Surgery, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan, ³ Core Research for Evolutional Science and Technology of Japan Science and Technology Corporation, Kawaguchi, Saitama, 332-0012, Japan, and ⁴ Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka 812-8582, Japan

The Rho family of small GTPases, key regulators of the actin cytoskeleton in eukaryotic cells from yeast to human, is implicated in the control of neuronal morphology. Guanine nucleotide exchange factors (GEFs) are upstream positive regulators of Rho GTPases and integrate extracellular signaling for appropriate activation of Rho GTPases at specific subcellular regions. Here we describe the identification of a novel Dbl family GEF for Rho GTPases in Homo sapiens and Mus musculus. It contains a tandem Dbl homology-pleckstrin homology domain and FERM domain, characteristic of the plasma membrane proteins linker. This gene, termed FERM domain including RhoGEF (FIR), was abundantly expressed in brain, lung, and testis, as well as embryonic hippocampal and cortical neurons. FIR was found to activate the biochemical pathway specific for Rac1 but not for RhoA or Cdc42. Ectopic expression of FIR in the cortical neurons resulted in significantly shortened neurites and excessive growth cones, presumably mediated by Rac1. These results suggest that FIR may regulate neurite remodeling by mediating the signaling pathways from membrane proteins to Rac.

Key words: Rac1; Rho guanine nucleotide exchange factor; FERM domain; cytoskeleton; neurite outgrowth; neuronal morphology

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22198504-10$05.00/0

This article has been cited by other articles:

				J. E. Self, F. Shawkat, C. T. Malpas, N. S. Thomas, C. M. Harris, P. R. Hodgkins, X. Chen, D. Trump, and A. J. Lotery Allelic Variation of the FRMD7 Gene in Congenital Idiopathic Nystagmus Arch Ophthalmol, September 1, 2007; 125(9): 1255 - 1263. [Abstract] [Full Text] [PDF]

				S. Baldassa, N. Gnesutta, U. Fascio, E. Sturani, and R. Zippel SCLIP, a Microtubule-destabilizing Factor, Interacts with RasGRF1 and Inhibits Its Ability to Promote Rac Activation and Neurite Outgrowth J. Biol. Chem., January 26, 2007; 282(4): 2333 - 2345. [Abstract] [Full Text] [PDF]

				T. Murata, H. Ohnishi, H. Okazawa, Y. Murata, S. Kusakari, Y. Hayashi, M. Miyashita, H. Itoh, P.-A. Oldenborg, N. Furuya, et al. CD47 Promotes Neuronal Development through Src- and FRG/Vav2-Mediated Activation of Rac and Cdc42 J. Neurosci., November 29, 2006; 26(48): 12397 - 12407. [Abstract] [Full Text] [PDF]

				E.-E. Govek, S. E. Newey, and L. Van Aelst The role of the Rho GTPases in neuronal development Genes & Dev., January 1, 2005; 19(1): 1 - 49. [Abstract] [Full Text] [PDF]

				Y. Miyamoto, J. Yamauchi, and H. Itoh Src Kinase Regulates the Activation of a Novel FGD-1-related Cdc42 Guanine Nucleotide Exchange Factor in the Signaling Pathway from the Endothelin A Receptor to JNK J. Biol. Chem., August 8, 2003; 278(32): 29890 - 29900. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help