β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis.

dc.contributor.author

Lee, Sang-Hyun

dc.contributor.author

Hollingsworth, Ryan

dc.contributor.author

Kwon, Hyeok-Yil

dc.contributor.author

Lee, Narae

dc.contributor.author

Chung, Chang Y

dc.date.accessioned

2020-06-17T01:22:18Z

dc.date.available

2020-06-17T01:22:18Z

dc.date.issued

2012-09

dc.date.updated

2020-06-17T01:22:16Z

dc.description.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.

dc.identifier.issn

0894-1491

dc.identifier.issn

1098-1136

dc.identifier.uri

https://hdl.handle.net/10161/21065

dc.language

eng

dc.publisher

Wiley

dc.relation.ispartof

Glia

dc.relation.isversionof

10.1002/glia.22355

dc.subject

Microglia

dc.subject

Cell Line

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Focal Adhesions

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Animals

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Mice

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Arrestins

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Adenosine Diphosphate

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Cell Adhesion

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Chemotaxis

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MAP Kinase Signaling System

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Phosphorylation

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Paxillin

dc.subject

beta-Arrestins

dc.subject

beta-Arrestin 2

dc.title

β-arrestin 2-dependent activation of ERK1/2 is required for ADP-induced paxillin phosphorylation at Ser(83) and microglia chemotaxis.

dc.type

Journal article

pubs.begin-page

1366

pubs.end-page

1377

pubs.issue

9

pubs.organisational-group

Duke Kunshan University

pubs.organisational-group

Duke Kunshan University Faculty

pubs.organisational-group

Duke

pubs.publication-status

Published

pubs.volume

60

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