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: 6882940
• 负责人: LISA M SEVILLA
• 金额: $ 0.55万
• 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/6882940
• 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）：皮肤屏障的创建， 人体与环境的最终区分， 角质形成细胞，其形成被称为皮质包膜的结构。的 皮质被膜是一层不溶性的蛋白质和脂质层， 角质形成细胞的细胞膜的内表面， 表皮如果皮质包膜不能正确形成， 对生物体的后果可能包括对以下疾病的易感性增加： 感染或致死，由于经表皮水分流失。角质化包膜 似乎是以一种受管制的方式组装的，然而， 它的几种组成蛋白在其形成中的作用是未知的。的 斑蛋白家族成员periplakin和envoplakin在终末表达， 分化角质形成细胞，并被认为形成支架， 组装了皮质信封。这些蛋白质的作用 将通过双重检查小鼠来确定皮质包膜组装 缺乏周斑蛋白和包斑蛋白表达。以进一步限定 周斑蛋白功能的机制，与周斑蛋白相互作用的蛋白质 将被识别。此外，特定的氨基酸所需的适当 将确定周斑蛋白的定位。最后，推定显性 将构建周斑蛋白的阴性形式以进一步确定其作用 在表皮中。总的来说，拟议的实验将有助于 了解角质化包膜组装机制。

项目成果

KazrinE is a desmosome-associated liprin that colocalises with acetylated microtubules.

KazrinE 是一种与桥粒相关的脂蛋白，与乙酰化微管共定位。

• DOI: 10.1242/jcs.047266
• 发表时间: 2009
• 期刊: Journal of cell science
• 影响因子: 4
• 作者: Nachat,Rachida;Cipolat,Sara;Sevilla,LisaM;Chhatriwala,Mariya;Groot,KarenR;Watt,FionaM
• 通讯作者: Watt,FionaM

Kazrin, a novel periplakin-interacting protein associated with desmosomes and the keratinocyte plasma membrane.

• DOI: 10.1083/jcb.200312123
• 发表时间: 2004-08-30
• 期刊: The Journal of cell biology
• 作者: Groot KR;Sevilla LM;Nishi K;DiColandrea T;Watt FM
• 通讯作者: Watt FM

KazrinA is required for axial elongation and epidermal integrity in Xenopus tropicalis.

KazrinA 是热带爪蟾轴向伸长和表皮完整性所必需的。

• DOI: 10.1002/dvdy.21557
• 发表时间: 2008
• 期刊: Developmental dynamics : an official publication of the American Association of Anatomists
• 作者: Sevilla,LisaM;Rana,AmerA;Watt,FionaM;Smith,JamesC
• 通讯作者: Smith,JamesC

Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier.

• DOI: 10.1083/jcb.200706187
• 发表时间: 2007-12-31
• 期刊: The Journal of cell biology
• 作者: Sevilla LM;Nachat R;Groot KR;Klement JF;Uitto J;Djian P;Määttä A;Watt FM
• 通讯作者: Watt FM