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J. Biol. Chem., Vol. 282, Issue 8, 5814-5824, February 23, 2007

This Article Full Text Full Text (PDF) All Versions of this Article: 282/8/5814    most recent M610767200v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal 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 Google Scholar Google Scholar Articles by Yanagida, K. Articles by Shimizu, T. Search for Related Content PubMed PubMed Citation Articles by Yanagida, K. Articles by Shimizu, T. Social Bookmarking                      What's this?

LPA₄/p2y₉/GPR23 Mediates Rho-dependent Morphological Changes in a Rat Neuronal Cell Line^*

Keisuke Yanagida, Satoshi Ishii¹, Fumie Hamano, Kyoko Noguchi, and Takao Shimizu

From the Department of Biochemistry and Molecular Biology, Faculty of Medicine, the University of Tokyo and the Precursory Research for Embryonic Science and Technology (PRESTO) of Japan Science and Technology Agency, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Lysophosphatidic acid (LPA) is a potent lipid mediator that evokes a variety of biological responses in many cell types via its specific G protein-coupled receptors. In particular, LPA affects cell morphology, cell survival, and cell cycle progression in neuronal cells. Recently, we identified p2y₉/GPR23 as a novel fourth LPA receptor, LPA₄ (Noguchi, K., Ishii, S., and Shimizu, T. (2003) J. Biol. Chem. 278, 25600-25606). To assess the functions of LPA₄ in neuronal cells, we used rat neuroblastoma B103 cells that lack endogenous responses to LPA. In B103 cells stably expressing LPA₄, we observed G_q/11-dependent calcium mobilization, but LPA did not affect adenylyl cyclase activity. In LPA₄ transfectants, LPA induced dramatic morphological changes, i.e. neurite retraction, cell aggregation, and cadherin-dependent cell adhesion, which involved Rho-mediated signaling pathways. Thus, our results demonstrated that LPA₄ as well as LPA₁ couple to G_q/11 and G_12/13, whereas LPA₄ differs from LPA₁ in that it does not couple to G_i/o. Through neurite retraction and cell aggregation, LPA₄ may play a role in neuronal development such as neurogenesis and neuronal migration.

Received for publication, June 21, 2006 , and in revised form, December 15, 2006.

^* This work was supported by grants-in-aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (to T. S. and S. I.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ To whom correspondence should be addressed: Dept. of Biochemistry and Molecular Biology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Tel.: 81-3-5802-2925; Fax: 81-3-3813-8732; E-mail: mame{at}m.u-tokyo.ac.jp.

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