Severe keratin 5 and 14 mutations induce down-regulation of junction proteins in keratinocytes

Mirjana Liovic, Mariella D'Alessandro, Marjana Tomic-Canic, Viacheslav N. Bolshakov, Stephanie E. Coats, E. Birgitte Lane

Research output: Contribution to journalArticle

32 Scopus citations

Abstract

The intermediate filament cytoskeleton is essential for the development and maintenance of normal tissue function. A number of diverse recent observations implicate these filament systems in sensing stress and protecting cells against its worst consequences. Cells expressing severely disruptive keratin mutations, characteristic of Dowling-Meara EBS, were previously reported to show elevated responses to physiological stress, and partial disassembly of cell junctions was reported upon direct mechanical stress to the cells. Gene expression microarray analysis has therefore been used here to examine the broad spectrum of effects of mutant keratins. Many genes associated with keratins and other components of the cytoskeleton showed altered expression levels; in particular, many cell junction components are down-regulated in EBS cells. That this is due to the expression of the mutant keratins, and not to other genetic variables, is supported by observation of the same effects in isogenic cells generated from wild type keratinocytes transfected with the same keratin mutations in the helix boundary motifs of K14 or K5. Whilst the mechanism underlying this is unclear, these findings may help to explain other aspects of EBS-associated pathology, such as faster scratch wound migration, or acantholysis (cell-cell separation) in patients' skin. Constitutive stress combined with constitutively weakened cell junctions may also contribute to a recently reported increased risk of non-melanoma skin cancer in EBS patients.

Original languageEnglish (US)
Pages (from-to)2995-3003
Number of pages9
JournalExperimental Cell Research
Volume315
Issue number17
DOIs
StatePublished - Oct 15 2009

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Keywords

  • Cell junctions
  • EBS
  • Expression
  • Keratin
  • Microarray
  • Mutation

ASJC Scopus subject areas

  • Cell Biology

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