title: Lysophosphatidic acid induces neurite branch formation through LPA3.
abstract: Although neurite branching is crucial for neuronal network formation after birth, its underlying mechanisms remain unclear. Here, we demonstrate that lysophosphatidic acid (LPA) stimulates neurite branching through a novel signaling pathway. Treatment of neuronal cell lines with LPA resulted in neurite branch formation when LPA(3) receptor was introduced. The effects of LPA were blocked by inhibition of G(q) signaling. Furthermore, expression of inhibitory mutants of the small GTPase Rnd2/Rho7 or an Rnd2 effector rapostlin abolished LPA(3)-mediated neurite branching. The LPA(3) agonist 2(S)-OMPT or LPA also induced axonal branch formation in hippocampal neurons, which was blocked by G(q) and Rnd2 pathway inhibition or LPA(3) knockdown. These findings suggest that the novel signaling pathway involving LPA(3), G(q), and Rnd2 may play an important role in neuronal network formation.
authors.affiliation: Division of Molecular Neurobiology, Department of Life Science, Kinki University, Higashiosaka, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Furuta
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamane
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Tsujiuchi
authors.forename: Ryutaro
authors.initials: R
authors.lastname: Moriyama
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Fukushima
mesh_terms: D016475:3T3 Cells; D000818:Animals; D043802:GTP-Binding Protein alpha Subunits, Gq-G11 / Q000378:metabolism; D008246:Lysophospholipids / Q000494:pharmacology*; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D016716:PC12 Cells; D034741:RNA, Small Interfering; D051381:Rats; D049368:Receptors, Lysophosphatidic Acid / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D034741:RNA, Small Interfering; D049368:Receptors, Lysophosphatidic Acid; C475019:Rnd2 protein, mouse; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D020741:rho GTP-Binding Proteins