Periplakin's role in assembly of the cornified envelope

Periplakin 在角质化包膜组装中的作用

• 批准号: 6626197
• 负责人: LISA M SEVILLA
• 金额: $ 3.61万
• 依托单位: IMPERIAL CANCER RESEARCH FUND
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-04-22 至 2005-04-21
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6626197
• 关键词: actins; cell component structure /function; cell differentiation; cell growth regulation; cell membrane; cytoskeletal proteins; cytoskeleton; developmental genetics; epithelium; fluorescence microscopy; genetically modified animals; immunofluorescence technique; intercellular connection; intermolecular interaction; keratinocyte; laboratory mouse; membrane structure; molecular assembly /self assembly; molecular site; postdoctoral investigator; protein localization; protein sequence; protein structure function; site directed mutagenesis; yeast two hybrid system

DESCRIPTION: (provided by applicant): The creation of the skin barrier between the human body and the environment is carried out by terminally differentiating keratinocytes, which form a structure known as the cornified envelope. The cornified envelope is an insoluble layer of proteins and lipids lining the inner surface of the plasma membrane of keratinocytes in the upper layers of the epidermis. If the cornified envelope is unable to properly form, the consequences for an organism may include an increased susceptibility to infection or lethality due to transepidermal water loss. The cornified envelope appears to be assembled in a regulated fashion, however the precise roles that several of its constituent proteins play in its formation are unknown. The plakin family members periplakin and envoplakin are expressed in terminally differentiating keratinocytes and are thought to form a scaffold on which the cornified envelope is assembled. The role(s) that these proteins play in cornified envelope assembly will be determined by examining the mice doubly deficient in periplakin and envoplakin expression. To further define the mechanism by which periplakin functions, proteins that interact with periplakin will be identified. Additionally, specific amino acids required for proper localization of periplakin will be determined. Finally, putative dominant negative forms of periplakin will be constructed to further determine its role in the epidermis. Overall, the proposed experiments will contribute to knowledge of the mechanism by which the cornified envelope is assembled.

描述：（由申请人提供）：在皮肤之间建立皮肤屏障 人体与环境是通过终末分化来进行的 角质形成细胞，形成称为角质化包膜的结构。这 角质化包膜是一层由蛋白质和脂质组成的不溶性层 上层角质形成细胞质膜的内表面 表皮。如果角质化包膜无法正常形成， 对有机体的后果可能包括增加对 由于经表皮失水而导致感染或死亡。角质化信封 似乎是以受监管的方式组装的，但是确切的角色 它的几种组成蛋白在其形成过程中发挥的作用尚不清楚。这 plakin 家族成员 periplakin 和 envoplakin 在末端表达 分化角质形成细胞，并被认为形成一个支架，在该支架上 角化信封已组装。这些蛋白质发挥的作用 角质化包膜组装将通过对小鼠进行双重检查来确定 周斑蛋白和包膜蛋白表达缺陷。为了进一步定义 Periplakin 发挥作用的机制、与 Periplakin 相互作用的蛋白质 将被识别。此外，适当的氨基酸需要特定的氨基酸。 将确定周斑蛋白的定位。最后，假定的主导 将构建 periplakin 的阴性形式以进一步确定其作用 在表皮中。总的来说，所提出的实验将有助于 了解角化包膜的组装机制。