α-Actinin-4 Is Essential for Maintaining the Spreading, Motility and Contractility of Fibroblasts

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α-Actinin-4 Is Essential for Maintaining the Spreading, Motility and Contractility of Fibroblasts

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dc.contributor.author Shao, Hanshuang
dc.contributor.author Wells, Alan
dc.contributor.author Wang, James H. C.
dc.contributor.author Pollak, Martin Russell
dc.date.accessioned 2011-03-08T18:44:31Z
dc.date.issued 2010
dc.identifier.citation Shao, Hanshuang, James H. C. Wang, Martin R. Pollak, and Alan Wells. 2010. α-Actinin-4 is essential for maintaining the spreading, motility and contractility of fibroblasts. PLoS ONE 5(11): e13921. en_US
dc.identifier.issn 1932-6203 en_US
dc.identifier.uri http://nrs.harvard.edu/urn-3:HUL.InstRepos:4739295
dc.description.abstract Background: α-Actinins cross-link actin filaments, with this cross-linking activity regulating the formation of focal adhesions, intracellular tension, and cell migration. Most non-muscle cells such as fibroblasts express two isoforms, α-actinin-1 (ACTN1) and α-actinin-4 (ACTN4). The high homology between these two isoforms would suggest redundancy of their function, but recent studies have suggested different regulatory roles. Interestingly, ACTN4 is phosphorylated upon growth factor stimulation, and this loosens its interaction with actin. Methodology/Principal Findings: Using molecular, biochemical and cellular techniques, we probed the cellular functions of ACTN4 in fibroblasts. Knockdown of ACTN4 expression in murine lung fibroblasts significantly impaired cell migration, spreading, adhesion, and proliferation. Surprisingly, knockdown of ACTN4 enhanced cellular compaction and contraction force, and increased cellular and nuclear cross-sectional area. These results, except the increased contractility, are consistent with a putative role of ACTN4 in cytokinesis. For the transcellular tension, knockdown of ACTN4 significantly increased the expression of myosin light chain 2, a element of the contractility machinery. Re-expression of wild type human ACTN4 in ACTN4 knockdown murine lung fibroblasts reverted cell spreading, cellular and nuclear cross-sectional area, and contractility back towards baseline, demonstrating that the defect was due to absence of ACTN4. Significance: These results suggest that ACTN4 is essential for maintaining normal spreading, motility, cellular and nuclear cross-sectional area, and contractility of murine lung fibroblasts by maintaining the balance between transcellular contractility and cell-substratum adhesion. en_US
dc.language.iso en_US en_US
dc.publisher Public Library of Science en_US
dc.relation.isversionof doi:10.1371/journal.pone.0013921 en_US
dc.relation.hasversion http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2978680/pdf/ en_US
dash.license LAA
dc.title α-Actinin-4 Is Essential for Maintaining the Spreading, Motility and Contractility of Fibroblasts en_US
dc.type Journal Article en_US
dc.description.version Version of Record en_US
dc.relation.journal PLoS ONE en_US
dash.depositing.author Pollak, Martin Russell
dc.date.available 2011-03-08T18:44:31Z
dash.affiliation.other HMS^Medicine- Beth Israel-Deaconess en_US

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