MATSUKI 1998:
[ Ссылка ]
[ Ссылка ]
[ Ссылка ]
[ Ссылка ]
[ Ссылка ]
[ Ссылка ]

Abstract
The stratum corneum of the skin serves as an effective barrier for maintenance of the internal milieu against the external environment.

At the cell periphery of the stratum corneum is the cell envelope, a highly insoluble membranous structure composed of precursor proteins cross-linked by epsilon-(gamma-glutamyl)lysine bonds.

Transglutaminase 1 (TGase 1; keratinocyte TGase), a membrane-bound isozyme of the TGase family, has been proposed to catalyze this process of assembly.

Deficient cross-linking of the cell envelope in some patients with the autosomal recessive skin disorder lamellar ichthyosis (LI) and several mutations of the TGase 1 gene that have been identified in families with LI suggest the importance of this gene in production of the cell envelope.

In this study, we generated mice lacking the TGase 1 gene, and we report that they have erythrodermic skin with abnormal keratinization.

In their stratum corneum, degradation of nuclei and keratohyalin F-granules was incomplete and cell envelope assembly was defective.

The skin barrier function of TGase 1-null mice was markedly impaired, and these mice died within 4-5 h after birth.

These results clearly demonstrate that the TGase 1 gene is essential to the development and maturation of the stratum corneum and to adaptation to the environment after birth.

Thus, these TGase 1 knockout mice may be a useful model for severe cases of LI.

HITOMI 2005
[ Ссылка ]

Skin functions as a stable, physical and chemical barrier from environmental influences (Hitomi 2005).

The cornified cell envelope (CE) is a critical structure for barrier function at the outermost layer of the skin epidermis (Hitomi 2005).

For CE formation in terminal keratinocyte differentiation, covalent cross-linking of constituting proteins such as involucrin, loricrin, small proline-rich protein is essential (Hitomi 2005).

This reaction requires transglutaminase (TGase), which is a calcium-dependent enzyme catalyzing an intermolecular isopeptide bond formation between proteins (Hitomi 2005).

Among the nine TGases that have been identified in humans, TGases 1, 3, and 5 are known to participate in CE formation (Hitomi 2005).

ECKERT 2005
[ Ссылка ]

A major function of the epidermis is protection of the organism from the environment (Eckert 2005).

The cornified envelope is a covalently cross-linked structure that forms beneath the plasma membrane in differentiating keratinocytes (Eckert 2005).

The envelope includes two functional parts—an insoluble 15 nm thick structure consisting of covalently cross-linked protein (10 nm thick) that comprises the backbone of the envelope and covalently linked lipids (5 nm thick) that coat the exterior (Eckert 2005).

Various proteins function as substrates and are incorporated into this structure. These include soluble (e.g., involucrin and small proline-rich proteins (SPR)) and insoluble (e.g., loricrin, periplakin, and envoplakin) proteins (Eckert 2005).

Several soluble precursors are initially deposited to form a scaffold (Eckert 2005).

The insoluble precursors are subsequently deposited on the inner surface of the scaffolding. For example, loricrin is a major protein of the envelope that is cross-linked to the inner surface of the scaffolding (Eckert 2005).

The interprotein cross-links that hold together this multiprotein assembly are formed by transglutaminases (TGase). TGase comprise a family of calcium-dependent enzymes that catalyze the formation of isopeptide bonds (Eckert 2005).

Three TGase are known to be active in surface epithelia and are thought to participate to varying degrees in cross-link formation. These include TGase 1, TGase 3, and TGase 5 (Eckert 2005).

свернуть