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Kindlin-1 regulates keratinocyte electrotaxis

Zhang, Gaofeng, Gu, Yu, Begum, Rumena, Chen, Hongduo, Gao, Xinghua, McGrath, John A., Parsons, Maddy and Song, Bing 2016. Kindlin-1 regulates keratinocyte electrotaxis. Journal of Investigative Dermatology 136 (11) , pp. 2229-2239. 10.1016/j.jid.2016.05.129

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Abstract

Kindler syndrome (KS) is an autosomal recessive blistering skin disease resulting from pathogenic mutations in FERMT1. This gene encodes kindlin-1, a focal adhesion protein involved in activation of the integrin family of extracellular matrix receptors. Most cases of KS show a marked reduction or complete absence of the kindlin-1 protein in keratinocytes, resulting in defective cell adhesion and migration. Electric fields also act as intrinsic regulators of adhesion and migration in the skin, but the molecular mechanisms by which this occurs are poorly understood. Here we show that keratinocytes derived from KS patients are unable to undergo electrotaxis, and this defect is restored by overexpression of wild-type kindlin-1 but not a W612A mutation that prevents kindlin-integrin binding. Moreover, deletion of the pleckstrin homology domain of kindlin-1 also failed to rescue electrotaxis in KS cells, indicating that both integrin and lipid binding are required for this function. Kindlin-1 was also required for the maintenance of lamellipodial protrusions during electrotaxis via electric field-activated β1 integrin. Indeed, inhibition of β1 integrins also leads to loss of electrotaxis in keratinocytes. Our data suggest that loss of kindlin-1 function may therefore result in epithelial insensitivity to electric fields and contribute to KS disease pathology.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Dentistry
Publisher: Elsevier
ISSN: 0022-202X
Last Modified: 31 Oct 2017 12:58
URI: http://orca.cf.ac.uk/id/eprint/93401

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