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

Kyoko Noguchi,Takao Shimizu,Fumie Hamano,Keisuke Yanagida,Satoshi Ishii

doi:10.1074/jbc.m610767200

Kyoko Noguchi, Takao Shimizu + Show 3 more

Open Access

https://doi.org/10.1074/jbc.m610767200

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Abstract

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 p2y(9)/GPR23 as a novel fourth LPA receptor, LPA(4) (Noguchi, K., Ishii, S., and Shimizu, T. (2003) J. Biol. Chem. 278, 25600-25606). To assess the functions of LPA(4) in neuronal cells, we used rat neuroblastoma B103 cells that lack endogenous responses to LPA. In B103 cells stably expressing LPA(4), we observed G(q/11)-dependent calcium mobilization, but LPA did not affect adenylyl cyclase activity. In LPA(4) 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 LPA(4) as well as LPA(1) couple to G(q/11) and G(12/13), whereas LPA(4) differs from LPA(1) in that it does not couple to G(i/o). Through neurite retraction and cell aggregation, LPA(4) may play a role in neuronal development such as neurogenesis and neuronal migration.

Highlights

Lysophosphatidic acid (LPA,2 1- or 2-acyl-sn-glycero-3phosphate) is a naturally occurring bioactive lipid mediator that controls growth, motility, and differentiation [1]
This study demonstrates that treatment of the LPA4-expressing cells with LPA leads to morphological changes, including cell rounding and cadherin-dependent cell adhesion following cell aggregation, both of which are mediated by the Rho/Rho-associated kinase (ROCK) pathway
As in the parental B103 cells, we observed only a low expression of LPA4 and virtually no expression of the other LPA receptors in all of the transfected cell lines. neuroblastoma cells were stably transfected with the expression these stably transfected cell lines showed similar vector for either LPA1 or LPA4

Summary

Introduction

Lysophosphatidic acid (LPA,2 1- or 2-acyl-sn-glycero-3phosphate) is a naturally occurring bioactive lipid mediator that controls growth, motility, and differentiation [1]. 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. The effects of LPA on target cells are mediated by activation of its specific G protein-coupled receptors (GPCRs).

Results

Conclusion