Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

J. Biol. Chem. 286 (7): 5157-5165

© 2011 by The American Society for Biochemistry and Molecular Biology, Inc.

Neogenin, a Receptor for Bone Morphogenetic Proteins*

Meiko Hagihara{ddagger}, Mitsuharu Endo{ddagger}, Katsuhiko Hata{ddagger}, Chikahisa Higuchi§, Kunio Takaoka, Hideki Yoshikawa§, , and Toshihide Yamashita{ddagger}||1

From the Departments of {ddagger}Molecular Neuroscience and
§Orthopedic Surgery, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871, Japan,
the Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka, Osaka 545-8585, Japan, and
||JST, CREST, 5, Sanbancho, Chiyoda-ku, Tokyo 102-0075, Japan

ABSTRACT Back to Top

Abstract: Bone morphogenetic proteins (BMPs) regulate many mammalian physiologic and pathophysiologic processes. These proteins bind with the kinase receptors BMPR-I and BMPR-II, thereby activating Smad transcription factor. In this study, we demonstrate that neogenin, a receptor for netrins and proteins of the repulsive guidance molecule family, is a receptor for BMPs and modulates Smad signal transduction. Neogenin was found to bind directly with BMP-2, BMP-4, BMP-6, and BMP-7. Knockdown of neogenin in C2C12 cells resulted in the enhancement of the BMP-2-induced processes of osteoblastic differentiation and phosphorylation of Smad1, Smad5, and Smad8. Conversely, overexpression of neogenin in C2C12 cells suppressed these processes. Our results also indicated that BMP-induced activation of RhoA was mediated by neogenin. Inhibition of RhoA promoted BMP-2-induced processes of osteoblastic differentiation and phosphorylation of Smad1/5/8. However, treatment with Y-27632, an inhibitor of Rho-associated protein kinase, did not modulate BMP-induced phosphorylation of Smad1/5/8. Taken together, our findings suggest that neogenin negatively regulates the functions of BMP and that this effect of neogenin is mediated by the activation of RhoA.


Key Words: Bone Morphogenetic Protein (BMP) • Differentiation • Rho • Signal Transduction • SMAD Transcription Factor

Received for publication September 1, 2010. Revision received November 5, 2010.

1 To whom correspondence should be addressed: Dept. of Molecular Neuroscience, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan. Tel.: 81-6-68793661; Fax: 81-6-68793669; E-mail: yamashita{at}molneu.med.osaka-u.ac.jp.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
The neogenin/DCC homolog UNC-40 promotes BMP signaling via the RGM protein DRAG-1 in C. elegans.
C. Tian, H. Shi, S. Xiong, F. Hu, W.-C. Xiong, and J. Liu (2013)
Development 140, 4070-4080
   Abstract »    Full Text »    PDF »
Neogenin Interacts with Matriptase-2 to Facilitate Hemojuvelin Cleavage.
C. A. Enns, R. Ahmed, and A.-S. Zhang (2012)
J. Biol. Chem. 287, 35104-35117
   Abstract »    Full Text »    PDF »
The guidance receptor neogenin promotes pulmonary inflammation during lung injury.
V. Mirakaj, C. Jennewein, K. Konig, T. Granja, and P. Rosenberger (2012)
FASEB J 26, 1549-1558
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882