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Actinin\u20104 associates with lamellipodia and has been implicated in regulating lamellipodial structure, function and assembly. To study the functions of actinin\u20104 in human keratinocytes, we used shRNA to generate knockdown cells and compared their motility behavior and matrix adhesion assembly to scrambled shRNA treated control keratinocytes. Actinin\u20104 knockdown keratinocytes lack polarity, assemble multiple lamellipodia with a 2\u00d7 increased area over controls, display reduced activity of the actin remodeling protein cofilin, and fail to migrate in a directional manner. This motility defect is rescued by plating knockdown cells on preformed laminin\u2010332 matrix. In actinin\u20104\u2010knockdown keratinocytes, focal contact area is increased by 25%, and hemidesmosome proteins are mislocalized. Specifically, \u03b16\u03b24 integrin localizes to large lamellipodial extensions, displays reduced dynamics, and fails to recruit its bullous pemphigoid antigen binding partners. Together, our data indicate a role for actinin\u20104 in regulating the steering mechanism of keratinocytes\n                    <jats:italic>via<\/jats:italic>\n                    profound effects on their matrix adhesion sites.\u2014Hamill, K. J., Hopkinson, S. B., Skalli, O., Jones, J. C. R. Actinin\u20104 in keratinocytes regulates motility\n                    <jats:italic>via<\/jats:italic>\n                    an effect on lamellipodia stability and matrix adhesions.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    27, 546\u2013556 (2013).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-217406","type":"journal-article","created":{"date-parts":[[2012,10,20]],"date-time":"2012-10-20T02:36:11Z","timestamp":1350700571000},"page":"546-556","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Actinin\u20104 in keratinocytes regulates motility\n                    <i>via<\/i>\n                    an effect on lamellipodia stability and matrix adhesions"],"prefix":"10.1096","volume":"27","author":[{"given":"Kevin J.","family":"Hamill","sequence":"first","affiliation":[{"name":"Department of Cell and Molecular Biology Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan B.","family":"Hopkinson","sequence":"additional","affiliation":[{"name":"Department of Cell and Molecular Biology Feinberg School of Medicine Northwestern University Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Omar","family":"Skalli","sequence":"additional","affiliation":[{"name":"Department of Biological Sciences University of Memphis Memphis Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan C. 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