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Lysophosphatidic acid receptor activation affects the C13NJ microglia cell line proteome leading to alterations in glycolysis, motility, and cytoskeletal architecture
Author(s) -
Bernhart Eva,
Kollroser Manfred,
Rechberger Gerald,
Reicher Helga,
Heinemann Akos,
Schratl Petra,
Hallström Seth,
Wintersperger Andrea,
Nusshold Christoph,
DeVaney Trevor,
ZornPauly Klaus,
Malli Roland,
Graier Wolfgang,
Malle Ernst,
Sattler Wolfgang
Publication year - 2009
Publication title -
proteomics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.26
H-Index - 167
eISSN - 1615-9861
pISSN - 1615-9853
DOI - 10.1002/pmic.200900195
Subject(s) - lysophosphatidic acid , microbiology and biotechnology , biology , microglia , motility , cytoskeleton , actin cytoskeleton , rhoa , cell migration , signal transduction , crosstalk , rac1 , receptor , cell , inflammation , biochemistry , immunology , physics , optics
Microglia, the immunocompetent cells of the CNS, are rapidly activated in response to injury and microglia migration towards and homing at damaged tissue plays a key role in CNS regeneration. Lysophosphatidic acid (LPA) is involved in signaling events evoking microglia responses through cognate G protein‐coupled receptors. Here we show that human immortalized C13NJ microglia express LPA receptor subtypes LPA 1 , LPA 2 , and LPA 3 on mRNA and protein level. LPA activation of C13NJ cells induced Rho and extracellular signal‐regulated kinase activation and enhanced cellular ATP production. In addition, LPA induced process retraction, cell spreading, led to pronounced changes of the actin cytoskeleton and reduced cell motility, which could be reversed by inhibition of Rho activity. To get an indication about LPA‐induced global alterations in protein expression patterns a 2‐D DIGE/LC‐ESI‐MS proteomic approach was applied. On the proteome level the most prominent changes in response to LPA were observed for glycolytic enzymes and proteins regulating cell motility and/or cytoskeletal dynamics. The present findings suggest that naturally occurring LPA is a potent regulator of microglia biology. This might be of particular relevance in the pathophysiological context of neurodegenerative disorders where LPA concentrations can be significantly elevated in the CNS.