HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 283, Issue 12, 7470-7479, March 21, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/12/7470    most recent M707758200v1 Submit a Letter to Editor 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 PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Spohr, T. C. d. S. e Articles by Chun, J. Search for Related Content PubMed PubMed Citation Articles by Spohr, T. C. d. S. e Articles by Chun, J. Social Bookmarking                      What's this?

Lysophosphatidic Acid Receptor-dependent Secondary Effects via Astrocytes Promote Neuronal Differentiation^*

Tânia Cristina de Sampaio e Spohr¹, Ji Woong Choi¹, Shannon E. Gardell, Deron R. Herr, Stevens Kastrup Rehen, Flávia Carvalho Alcantara Gomes², and Jerold Chun³

From the Departamento de Anatomia, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, 21949-590 Rio de Janeiro RJ, Brazil and the Department of Molecular Biology, Helen L. Dorris Child and Adolescent Neuropsychiatric Disorder Institute, The Scripps Research Institute, La Jolla, California 92037

Lysophosphatidic acid (LPA) is a simple phospholipid derived from cell membranes that has extracellular signaling properties mediated by at least five G protein-coupled receptors referred to as LPA₁–LPA₅. In the nervous system, receptor-mediated LPA signaling has been demonstrated to influence a range of cellular processes; however, an unaddressed aspect of LPA signaling is its potential to produce specific secondary effects, whereby LPA receptor-expressing cells exposed to, or "primed," by LPA may then act on other cells via distinct, yet LPA-initiated, mechanisms.

In the present study, we examined cerebral cortical astrocytes as possible indirect mediators of the effects of LPA on developing cortical neurons. Cultured astrocytes express at least four LPA receptor subtypes, known as LPA₁–LPA₄. Cerebral cortical astrocytes primed by LPA exposure were found to increase neuronal differentiation of cortical progenitor cells. Treatment of unprimed astrocyte-progenitor cocultures with conditioned medium derived from LPA-primed astrocytes yielded similar results, suggesting the involvement of an astrocyte-derived soluble factor induced by LPA. At least two LPA receptor subtypes are involved in LPA priming, since the priming effect was lost in astrocytes derived from LPA receptor double-null mice (). Moreover, the loss of LPA-dependent differentiation in receptor double-null astrocytes could be rescued by retrovirally transduced expression of a single deleted receptor. These data demonstrate that receptor-mediated LPA signaling in astrocytes can induce LPA-dependent, indirect effects on neuronal differentiation.

Received for publication, September 17, 2007 , and in revised form, December 20, 2007.

^* This work was supported by grants from the Third World Academy of Science (to F. G.), Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (to F. G. and T. S.), Conselho Nacional para o Desenvolvimento Científico e Tecnológico (to F. G. and S. R.), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES (to T. S.), the Pew Latin American Program in Biomedical Sciences (to S. R.), and National Institutes of Health Grants MH051699 and NS048478 (to J. C.). 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.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Table 1.

¹ Both authors contributed equally to this work.

² To whom correspondence may be addressed. E-mail: fgomes{at}anato.ufrj.br. ³ To whom correspondence may be addressed: The Scripps Research Institute, ICND 118, 10550 N. Torrey Pines Rd., La Jolla, CA 92037. E-mail: jchun{at}scripps.edu.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				S.-J. Lee, T.-H. Chan, T.-C. Chen, B.-K. Liao, P.-P. Hwang, and H. Lee LPA1 is essential for lymphatic vessel development in zebrafish FASEB J, October 1, 2008; 22(10): 3706 - 3715. [Abstract] [Full Text] [PDF]