Plectin isoform-dependent regulation of keratin-integrin α6β4 anchorage via Ca2+/calmodulin

Abstract

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 la 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 la is first relocated within the cell and later down-regulated, suggesting that Ca2+ affects the late ofplectin la 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 la and phosphorytation of integrin β4 by protein kinases, are required for disruption of the integrin αβ6β4-plectin complex.