β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis.
Abstract
Microglia play crucial roles in increased inflammation in the central nervous system
upon brain injuries and diseases. Extracellular ADP has been reported to induce microglia
chemotaxis and membrane ruffle formation through P2Y(12) receptor. In this study,
we examined the role of ERK1/2 activation in ADP-induced microglia chemotaxis. ADP
stimulation increases the phosphorylation of extracellular signal-regulated kinase
1/2 (ERK1/2) and paxillin phosphorylation at Tyr(31) and Ser(83) . Inhibition of ERK1/2
significantly inhibited paxillin phosphorylation at Ser(83) and the retraction of
membrane ruffles, causing inefficient chemotaxis. Close examination of dynamics of
focal adhesion (FA) formation with green fluorescent protein-paxillin revealed that
the disassembly of FAs in U0126-treated cells was significantly impaired. Depletion
of β-Arrestin 2 (β-Arr2) with short hairpin RNA markedly reduced the phosphorylation
of ERK1/2 and Pax/Ser(83) , indicating that β-Arr2 is required for ERK1/2 activation
upon ADP stimulation. A large fraction of phosphorylated ERK1/2 and β-Arr2 were translocated
and co-localized at focal contacts in the newly forming lamellipodia. Examination
of kinetics and rate constant of paxillin formation and disassembly revealed that
the phosphorylation of paxillin at Tyr(31) by c-Src appears to be involved in adhesion
formation upon ADP stimulation while Ser(83) required for adhesion disassembly.
Type
Journal articleSubject
MicrogliaCell Line
Focal Adhesions
Animals
Mice
Arrestins
Adenosine Diphosphate
Cell Adhesion
Chemotaxis
MAP Kinase Signaling System
Phosphorylation
Paxillin
beta-Arrestins
beta-Arrestin 2
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https://hdl.handle.net/10161/21065Published Version (Please cite this version)
10.1002/glia.22355Publication Info
Lee, Sang-Hyun; Hollingsworth, Ryan; Kwon, Hyeok-Yil; Lee, Narae; & Chung, Chang Y (2012). β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation
at Ser(83) and microglia chemotaxis. Glia, 60(9). pp. 1366-1377. 10.1002/glia.22355. Retrieved from https://hdl.handle.net/10161/21065.This is constructed from limited available data and may be imprecise. To cite this
article, please review & use the official citation provided by the journal.
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Chang Yong Chung
Professor of Biology at Duke Kunshan University

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