LPA4/p2y9/GPR23 mediates rho-dependent morphological changes in a rat neuronal cell line.
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.
Yanagida
Keisuke
K
Department of Biochemistry and Molecular Biology, Faculty of Medicine, the University of Tokyo, Tokyo 113-0033, Japan.
Ishii
Satoshi
S
Hamano
Fumie
F
Noguchi
Kyoko
K
Shimizu
Takao
T
D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000235:genetics; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D048430:Cell Shape / Q000187:drug effects / Q000235:genetics; D044365:GTP-Binding Protein alpha Subunits, G12-G13 / Q000378:metabolism*; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism*; D008246:Lysophospholipids / Q000494:pharmacology*; D016501:Neurites / Q000378:metabolism*; D051381:Rats; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid
D000262:Adenylyl Cyclases; D015820:Cadherins; D044365:GTP-Binding Protein alpha Subunits, G12-G13; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D008246:Lysophospholipids; D018048:Receptors, Purinergic P2; C518825:Lpar4 protein, rat; D049368:Receptors, Lysophosphatidic Acid; C032881:lysophosphatidic acid