角化過程の理解と角化異常症, 最近の到達点 Recent advances in understanding of keratinization and keratinization disorders

著者版Recently there have been great advances in molecular understanding of two major keratinization disorders, loricrin keratoderma (LK) and ichthyosis hystrix, Curth-Macklin type (IHCM). In LK, the unique heterozygous mutations in the glycine-rich domain of the mutant loricrin form arginine-rich nuclear localization sequences that likely to disrupt differentiation of keratinocytes. In IHCM, a heterozygous frameshift mutation in the tail domain of K1 leads to specific cytoskeletal abnormalities in the differentiated keratinocytes. Present classification of keratinization disorders mainly based on clinical manifestations has to be modified based on recent findings in the molecular mechanisms. As to discoveries in basics of keratinization, we have recently proposed a new model of lemellar granules based on immunoelectron microscopic analysis. In this model, lemellar granules are parts of a branched tubular structure, where various lamellar granule cargoes are sequentially synthesized and independently transported from the trans-Golgi network.