Lysophosphatidic acid receptor activation affects the C13NJ microglia cell line proteome leading to alterations in glycolysis, motility, and cytoskeletal architecture.
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.
Bernhart
Eva
E
Institute of Molecular Biology and Biochemistry, Medical University of Graz, Austria.
Kollroser
Manfred
M
Rechberger
Gerald
G
Reicher
Helga
H
Heinemann
Akos
A
Schratl
Petra
P
Hallström
Seth
S
Wintersperger
Andrea
A
Nusshold
Christoph
C
DeVaney
Trevor
T
Zorn-Pauly
Klaus
K
Malli
Roland
R
Graier
Wolfgang
W
Malle
Ernst
E
Sattler
Wolfgang
W
D002460:Cell Line; D002465:Cell Movement; D003599:Cytoskeleton / Q000378:metabolism*; D005786:Gene Expression Regulation; D006019:Glycolysis; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism; D017628:Microglia / Q000166:cytology* / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020543:Proteome / Q000378:metabolism*; D049368:Receptors, Lysophosphatidic Acid / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D020741:rho GTP-Binding Proteins / Q000378:metabolism
D008246:Lysophospholipids; D020543:Proteome; D049368:Receptors, Lysophosphatidic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020741:rho GTP-Binding Proteins; C032881:lysophosphatidic acid