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J. Neurosci. 25 (6): 1343-1353

Copyright © 2005 by the Society for Neuroscience.


A Truncated Tropo-Myosine-Related Kinase B Receptor, T1, Regulates Glial Cell Morphology via Rho GDP Dissociation Inhibitor 1

Koji Ohira,1,2 Haruko Kumanogoh,1 Yoshinori Sahara,1 Koichi J. Homma,3 Hirohisa Hirai,2 Shun Nakamura,1 , and Motoharu Hayashi2

1Department of Biochemistry and Cellular Biology, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan, 2Department of Cellular and Molecular Biology, Primate Research Institute, Kyoto University, Inuyama, Aichi 484-8506, Japan, and 3Department of Molecular Pathology, Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa 199-0195, Japan

Abstract: Through tropo-myosine-related kinase B (TrkB) receptors, brain-derived neurotrophic factor (BDNF) performs many biological functions such as neural survival, differentiation, and plasticity. T1, an isoform of TrkB receptors that lacks a tyrosine kinase, predominates in the adult mammalian CNS, yet its role remains controversial. In this study, to examine whether T1 transduces a signal and to determine its function, we first performed an affinity purification of T1-binding protein with the T1-specific C-terminal peptide and identified Rho GDP dissociation inhibitor 1 (GDI1), a GDP dissociation inhibitor of Rho small G-proteins, as a signaling protein directly associated with T1. The binding of BDNF to T1 caused Rho GDI1 to dissociate from the C-terminal tail of T1. Astrocytes cultured for 30 d expressed only endogenous T1 among the BDNF receptors. In 30 d cultured astrocytes, Rho GDI1, when dissociated in a BDNF-dependent manner, controlled the activities of the Rho GTPases, which resulted in rapid changes in astrocytic morphology. Furthermore, using 2 d cultured astrocytes that were transfected with T1, a T1 deletion mutant, or cyan fluorescent protein fusion protein of the T1-specific C-terminal sequence, we demonstrated that T1-Rho GDI1 signaling was indispensable for regulating the activities of Rho GTPases and for the subsequent morphological changes among astrocytes. Therefore, these findings indicate that the T1 signaling cascade can alter astrocytic morphology via regulation of Rho GTPase activity.

Key Words: astrocyteBDNFprimary cultureRho GDIRho GTPasetruncated TrkBT1

Received for publication May 26, 2004. Revision received December 20, 2004. Accepted for publication December 22, 2004.

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