Periplakin's role in assembly of the cornified envelope

描述：(申请人提供)：创建皮肤屏障之间 人体与环境是通过终极分化来实现的 角质形成细胞，形成一种称为角化包膜的结构。这个 角化的包膜是一层不溶于水的蛋白质和脂类，包裹在 角质形成细胞上层质膜的内表面 表皮。如果角化的信封无法正确形成，则 对生物体的后果可能包括增加对 由于经表皮失水而感染或致死。角化的信封 似乎是以受监管的方式组装的，然而， 它的几个组成蛋白在它的形成中发挥作用尚不清楚。这个 Plakin家族成员periplakin和envoplakin在末端表达 分化角质形成细胞，并被认为形成了支架，在其上 角化的信封组装好了。这些蛋白质所扮演的角色(S) 角化的信封组件将通过双重检查老鼠来确定 缺乏周斑蛋白和包膜蛋白的表达。为了进一步定义 周斑蛋白的作用机制，即与周斑蛋白相互作用的蛋白质 将会被确认。此外，正常饮食所需的特定氨基酸 Periplakin的定位将被确定。最后，假定占主导地位 将构建阴性形式的周斑蛋白，以进一步确定其作用 在表皮中。总体而言，拟议的实验将有助于 关于组装角化信封的机制的知识。

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.