EXPRESSION, STRUCTURE AND FUNCTION OF FILAGGRIN

微丝蛋白是哺乳动物终末分化的主要产物 被认为参与聚集的表皮细胞和 角蛋白中间丝在最后阶段的特异性排列 分化阶段。因此，Filaggrin是一个重要的例子 一种与细丝相关的中间蛋白质。我们已经分离出两个cDNA 和基因组克隆，表明微丝蛋白最初表达为 一种大的多聚蛋白前体Profilaggrin，它随后被 蛋白水解物加工成单独的功能性微丝蛋白分子。 人类Profilaggrin基因的结构现在已经确定； 它由3个外显子组成，由2个内含子隔开，第一个内含子是巨大的 (约10KBP)。人和小鼠ProfilagGRin的氨基末端 具有两个EF-HAND类型的功能钙结合结构域。 有证据表明内含子和外显子的多重交替剪接， 产生了一系列其他的钙结合蛋白 未知函数。我们已经为生产构建了基因组克隆 转基因小鼠。我们已经开始对监管机构进行系统分析 控制profilaggrin基因系统表达的序列。 我们已经确定微丝蛋白聚集角蛋白和波形蛋白 通过离子相互作用产生的中间纤维。

Filaggrin is a major product of terminally differentiating mammalian epidermal cells that is thought to be involved in the aggregation and specific alignment of keratin intermediate filaments during the final stages of differentiation. Thus, filaggrin is an important example of an intermediate filament-associated protein. We have isolated both CDNA and genomic clones which show that filaggrin is expressed initially as a large polyprotein precursor, profilaggrin, which is subsequently proteolytically processed into individual functional filaggrin molecules. The structure of the gene for human profilaggrin has now been settled; it consists of 3 exons separated by 2 introns, the first of which is huge (about 10 kbp). The amino-terminal end of human and mouse profilaggrins possess two functional calcium-binding domains of the EF-hand type. There is evidence for multiple alternate splicing of introns and exons, giving rise to a series of other calcium-binding proteins of as yet unknown function. We have constructed genomic clones for the production of transgenic mice. We have begun a systemic analysis of regulatory sequences that control the expression of the profilaggrin gene system. We have determined that filaggrin aggregates keratin and vimentin intermediate filaments by ionic interactions.