Kostan Julius, Gregor Martin, Walko Gernot, Wiche Gerhard
Department of Molecular Cell Biology, Max F. Perutz Laboratories, University of Vienna, Vienna A-1030, Austria.
J Biol Chem. 2009 Jul 3;284(27):18525-36. doi: 10.1074/jbc.M109.008474. Epub 2009 May 6.
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.
在伤口愈合和角质形成细胞分化过程中，上皮细胞与基底膜分离需要半桥粒多蛋白黏附复合体的解体。整合素α6β4-网蛋白相互作用在半桥粒形成中起主要作用，因此调节这种相互作用的机制对于解体过程也至关重要。在此我们表明，一种特定的网蛋白异构体（1a）以钙依赖的方式与钙传感蛋白钙调蛋白相互作用。这种相互作用的结果是，与半桥粒相关的网蛋白异构体1a与整合素β4的结合显著减少。钙调蛋白结合还抑制网蛋白与F-肌动蛋白的相互作用。此外，我们发现，在钙诱导的角质形成细胞分化过程中，网蛋白1a首先在细胞内重新定位，随后表达下调，这表明钙在网蛋白1a从半桥粒释放后影响其命运。我们提出了一种角质形成细胞分化过程中半桥粒解体的新模型，其中钙调蛋白与网蛋白1a的结合以及蛋白激酶对整合素β4的磷酸化都是破坏整合素α6β4-网蛋白复合体所必需的。
