Plectin isoform-dependent regulation of keratin-integrin alpha6beta4 anchorage via Ca2+/calmodulin

Julius Kostan, Martin Gregor, Gernot Walko, Gerhard Wiche

Research output: Contribution to journalArticlepeer-review

43 Citations (SciVal)


The detachment of epithelial cells from the basal matrix during wound healing and differentiation of keratinocytes requires the disassembly of the hemidesmosomal multiprotein adhesion complex. Integrin alpha6beta4-plectin interaction plays a major role in the formation of hemidesmosomes, and thus the mechanisms regulating this interaction should be critical also for the disassembly process. Here we show that a particular plectin isoform (1a) interacts with the Ca(2+)-sensing protein calmodulin in a Ca(2+)-dependent manner. As a result of this interaction, binding of the hemidesmosome-associated plectin isoform 1a to integrin beta4 is substantially diminished. Calmodulin-binding inhibits also the interaction of plectin with F-actin. Further, we found that, during Ca(2+)-induced keratinocyte differentiation, plectin 1a is first relocated within the cell and later down-regulated, suggesting that Ca(2+) affects the fate of plectin 1a upon its release from hemidesmosomes. We propose a novel model for the disassembly of hemidesmosomes during keratinocyte differentiation, where both, binding of calmodulin to plectin 1a and phosphorylation of integrin beta4 by protein kinases, are required for disruption of the integrin alpha6beta4-plectin complex.

Original languageEnglish
Pages (from-to)18525-36
Number of pages12
JournalThe Journal of biological chemistry
Issue number27
Early online date6 May 2009
Publication statusPublished - 3 Jul 2009


  • Actins/metabolism
  • Animals
  • Calcium/metabolism
  • Calmodulin/metabolism
  • Cell Differentiation/physiology
  • Cells, Cultured
  • Down-Regulation/physiology
  • Hemidesmosomes/metabolism
  • Integrin alpha6beta4/genetics
  • Isomerism
  • Keratinocytes/cytology
  • Keratins/metabolism
  • Mice
  • Plectin/chemistry
  • Protein Structure, Tertiary
  • Rabbits
  • Swine
  • Transfection


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