Lysophosphatidic Acid Receptor Activation Affects the C13NJ Microglia Cell Line Proteome Leading to Alterations in Glycolysis, Motility, and Cytoskeletal Architecture

Overview

Journal Proteomics

Date 2009 Nov 10

PMID 19899077

Citations 42

Authors

Eva Bernhart

Manfred Kollroser

Gerald Rechberger

Helga Reicher

Akos Heinemann

Petra Schratl

Seth Hallstrom

Andrea Wintersperger

Christoph Nusshold

Trevor Devaney

Klaus Zorn-Pauly

Roland Malli

Wolfgang Graier

Ernst Malle

Wolfgang Sattler

Affiliations

Soon will be listed here.

Abstract

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.

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