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Kindlin-1 Regulates Keratinocyte Electrotaxis

Research output: Contribution to journalArticlepeer-review

Gaofeng Zhang, Yu Gu, Rumena Begum, Hongduo Chen, Xinghua Gao, John A. McGrath, Maddy Parsons, Bing Song

Original languageEnglish
Pages (from-to)2229-2239
Number of pages11
JournalJournal of Investigative Dermatology
Issue number11
Early online date15 Jul 2016
Accepted/In press10 May 2016
E-pub ahead of print15 Jul 2016
Published1 Nov 2016


King's Authors


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.

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