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Cell biological analyses of cornified cell envelope formation

角质化细胞包膜形成的细胞生物学分析

基本信息

批准号：
10470184
负责人：
YAMAMOTO Akemi
金额：
$ 2.69万
依托单位：
ASAHIKAWA MEDICAL COLLEGE
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

项目摘要

1. Loricrin keratoderma and cornified cell envelope formationLoricrin is the major constituent of cornified cell envelopes. We have discovered keratinization disorders caused by mutations of the loricrin gene and proposed the term 'loricrin keratoderma' for this unique group of diseases (J Dermatol Sci, 1999, Exp Dermatol, 1998, Histol Histopathol, 1998, J Dermatol Sci, 1998). We also raised antibodies against synthetic peptides corresponding to the mutated sequences of patients' loricrin gene. We have detected mutant loricrin in the nuclei of differentiated epidermal cells in the patient skin. Mutant loricrin was not detected on the cornified cell envelopes. This suggests that mutant loricrin has a dominant negative effect not on cornified cell envelope assembly itself, but on some nuclear functions (J Invest Dermatol, 2000).2. Subcellular localization of amino-terminal domain of profilaggrinIt has been suggested that amino-terminal domain of profilaggrin functions as a component of cornified cell envelopes. We have, however, detected nuclear localization of this domain in the terminally differentiated keratinocytes (Lab Invest 1998).3. Regulation of expression of the genes for involucrin and cystatin AWe have revealed regulatory mechanisms for the genes encoding involucrin and cystat in A, both are components of cornified cell envelopes (J Invest Dermatol, 1998, J Bi ol Chem, 1998, Biochem, 1999, BBRC, 2000).4. Epitope masking in cornified cell envelope formationWe have shown that loricrin epitopes have been masked at the desmosome areas in the matured cornified cell envelopes by developing a new immunoelectron microscopy technique (Exp Dermatol 1999).

1. Loricrin与角化细胞包膜形成Loricrin是角化细胞包膜的主要成分。我们发现了由loricrin基因突变引起的角化疾病，并提出了“loricrin角化病”一词来形容这类独特的疾病（J Dermatol Sci, 1999, Exp Dermatol, 1998, Histol Histopathol, 1998, J Dermatol Sci, 1998）。我们还提出了针对与患者氯胺基因突变序列相对应的合成肽的抗体。我们在患者皮肤的分化表皮细胞的细胞核中检测到突变的loricrin。在凝固的细胞包膜上未检测到突变体loricrin。这表明，突变体loricrin的主要负面影响不是对角质细胞包膜组装本身，而是对某些核功能（J Invest Dermatol, 2000）。profilaggrin氨基末端结构域的亚细胞定位研究表明，profilaggrin氨基末端结构域是凝固细胞包膜的一个组成部分。然而，我们已经在最终分化的角质形成细胞中检测到该结构域的核定位（Lab Invest 1998）。3 .我们已经揭示了A细胞中编码involucrin和cy抑素基因的调控机制，这两个基因都是凝固细胞包膜的组成部分（J Invest Dermatol, 1998, J Bi ol Chem, 1998, Biochem, 1999， BBRC, 2000）。我们通过开发一种新的免疫电子显微镜技术发现，loricrin表位在成熟的角化细胞包膜的桥粒区域被掩盖（Exp Dermatol 1999）。