title: TRPM2 mediates the lysophosphatidic acid-induced neurite retraction in the developing brain.
abstract: Intracellular Ca(2+) signal is a key regulator of axonal growth during brain development. As transient receptor potential (TRP) channels are permeable to Ca(2+) and mediate numerous brain functions, it is conceivable that many TRP channels would regulate neuronal differentiation. We therefore screened TRP channels that are involved in the regulation of neurite growth. Among the TRP channels, the Trpm2 level was inversely associated with neurite growth. TRPM2 was highly expressed in embryonic brain. Pharmacological perturbation or knockdown of TRPM2 markedly increased the axonal growth, whereas its overexpression inhibited the axonal growth. Addition of ADP ribose, an endogenous activator of TRPM2, to PC12 cells significantly repressed the axonal growth. TRPM2 was actively involved in the neuronal retraction induced by cerebrospinal fluid-rich lysophosphatidic acid (LPA). More importantly, neurons isolated from the brain of Trpm2-deficient mice have significantly longer neurites with a greater number of spines than those obtained from the brain of wild-type mice. Therefore, we conclude that TRPM2 mediates the LPA-induced suppression of axonal growth, which provides a long-sought mechanism underlying the effect of LPA on neuronal development.
authors.affiliation: Channel Research Center, CRI, College of Pharmacy, Seoul National University, 1 Gwanak-ro, Gwanak-gu, Seoul, 151-742, Republic of Korea.
authors.forename: Yongwoo
authors.initials: Y
authors.lastname: Jang
authors.forename: Mi Hyun
authors.initials: MH
authors.lastname: Lee
authors.forename: Jesun
authors.initials: J
authors.lastname: Lee
authors.forename: Jooyoung
authors.initials: J
authors.lastname: Jung
authors.forename: Sung Hoon
authors.initials: SH
authors.lastname: Lee
authors.forename: Dong-Jin
authors.initials: DJ
authors.lastname: Yang
authors.forename: Byung Woo
authors.initials: BW
authors.lastname: Kim
authors.forename: Hyeon
authors.initials: H
authors.lastname: Son
authors.forename: Boyoon
authors.initials: B
authors.lastname: Lee
authors.forename: Sunghoe
authors.initials: S
authors.lastname: Chang
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Mori
authors.forename: Uhtaek
authors.initials: U
authors.lastname: Oh
mesh_terms: D000246:Adenosine Diphosphate Ribose / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000166:cytology / Q000196:embryology / Q000378:metabolism*; D002478:Cells, Cultured; D057809:HEK293 Cells; D006801:Humans; D008246:Lysophospholipids / Q000494:pharmacology; D051379:Mice; D016501:Neurites / Q000187:drug effects / Q000378:metabolism*; D055495:Neurogenesis; D016716:PC12 Cells; D051381:Rats; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D008246:Lysophospholipids; D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse; D000246:Adenosine Diphosphate Ribose; C032881:lysophosphatidic acid