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The Journal of Neuroscience, November 29, 2006, 26(48):12397-12407; doi:10.1523/JNEUROSCI.3981-06.2006

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Cellular/Molecular
CD47 Promotes Neuronal Development through Src- and FRG/Vav2-Mediated Activation of Rac and Cdc42

Takaaki Murata,^1,2 Hiroshi Ohnishi,¹ Hideki Okazawa,¹ Yoji Murata,¹ Shinya Kusakari,¹ Yuriko Hayashi,¹ Motoaki Miyashita,¹ Hiroshi Itoh,³ Per-Arne Oldenborg,⁴ Nobuhiko Furuya,² and Takashi Matozaki¹

¹Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Gunma 371-8512, Japan, ²Department of Otolaryngology, Gunma University Graduate School of Medicine, Gunma 371-8511, Japan, ³Department of Cell Biology, Graduate School of Biological Sciences, Nara Institute of Science and Technology, Ikoma, Nara 630-0192, Japan, and ⁴Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, S-901 87 Umeå, Sweden

Correspondence should be addressed to Takashi Matozaki, Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan. Email: matozaki{at}showa.gunma-u.ac.jp

The development of axons and dendrites is controlled by small GTP-binding proteins of the Rho family, but the upstream signaling mechanisms responsible for such regulation remain unclear. We have now investigated the role of the transmembrane protein cluster of differentiation 47 (CD47) in this process with hippocampal neurons. CD47-deficient neurons manifested markedly impaired development of dendrites and axons, whereas overexpression of CD47 promoted such development. Interaction of SH2 domain-containing protein tyrosine phosphatase substrate-1 (SHPS-1) with CD47 also induced the formation of dendritic filopodia and spines. These effects of CD47 were prevented by inhibition of either cell division cycle 42 (Cdc42) or Rac. In CD47-deficient neurons, autophosphorylation of Src was markedly reduced. In addition, overexpression of CD47 promoted the autophosphorylation of Src. Inhibition of Src family kinases indeed prevented CD47-promoted dendritic development. Inhibition of either FGD1-related Cdc42-guanine nucleotide exchange factor (GEF) (FRG) or Vav2, which is a GEF for Cdc42 and Rac and is activated by Src, also prevented the effects of CD47 on dendritic development. These results indicate that CD47 promotes development of dendrites and axons in hippocampal neurons in a manner dependent, at least in part, on activation of Cdc42 and Rac mediated by Src as well as by FRG and Vav2.

Key words: dendrite; Src; small GTP-binding protein; guanine nucleotide exchange factor; SHPS-1; hippocampus

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Received June 6, 2006; accepted Oct. 13, 2006.

Correspondence should be addressed to Takashi Matozaki, Laboratory of Biosignal Sciences, Institute for Molecular and Cellular Regulation, Gunma University, 3-39-15 Showa-Machi, Maebashi, Gunma 371-8512, Japan. Email: matozaki{at}showa.gunma-u.ac.jp

This article has been cited by other articles:

				S. Kusakari, H. Ohnishi, F.-J. Jin, Y. Kaneko, T. Murata, Y. Murata, H. Okazawa, and T. Matozaki Trans-endocytosis of CD47 and SHPS-1 and its role in regulation of the CD47-SHPS-1 system J. Cell Sci., April 15, 2008; 121(8): 1213 - 1223. [Abstract] [Full Text] [PDF]

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