Plectin Isoform-dependent Regulation of Keratin-Integrin α6β4 Anchorage via Ca2+/Calmodulin*

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 α6β4-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 Ca2+-sensing protein calmodulin in a Ca2+-dependent manner. As a result of this interaction, binding of the hemidesmosome-associated plectin isoform 1a to integrin β4 is substantially diminished. Calmodulin-binding inhibits also the interaction of plectin with F-actin. Further, we found that, during Ca2+-induced keratinocyte differentiation, plectin 1a is first relocated within the cell and later down-regulated, suggesting that Ca2+ 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 β4 by protein kinases, are required for disruption of the integrin α6β4-plectin complex.

• Publication year

  2009

• Venue

  Journal of Biological Chemistry

• Publication date

  2009-05-06

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1074/jbc.M109.008474PMID 19419971PMCID PMC2709376
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Plectin.

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