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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
1F32HD042379-01X1
Application #
6574240
Study Section
Special Emphasis Panel (ZRG1 (20))
Program Officer
Javois, Lorette Claire
Project Start
2002-04-22
Project End
Budget Start
2002-04-22
Budget End
2003-04-21
Support Year
1
Fiscal Year
2002
Total Cost
$5,500
Indirect Cost
Name
Imperial Cancer Research Fund
Department
Type
DUNS #
City
London
State
Country
United Kingdom
Zip Code
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Sevilla, Lisa M; Nachat, Rachida; Groot, Karen R et al. (2008) Kazrin regulates keratinocyte cytoskeletal networks, intercellular junctions and differentiation. J Cell Sci 121:3561-9
Sevilla, Lisa M; Nachat, Rachida; Groot, Karen R et al. (2007) Mice deficient in involucrin, envoplakin, and periplakin have a defective epidermal barrier. J Cell Biol 179:1599-612
Groot, Karen R; Sevilla, Lisa M; Nishi, Kazunori et al. (2004) Kazrin, a novel periplakin-interacting protein associated with desmosomes and the keratinocyte plasma membrane. J Cell Biol 166:653-9