The cornified cell envelope: loricrin and transglutaminases

Abstract

The cornified cell envelope (CE) of terminally differentiated human epidermis is a complex structure consisting of several defined protein constituents. The CE is the most insoluble component of the epidermis due to crosslinking by disulfide bonds as well as isodipeptide bonds that are formed by the action of transglutaminases (TGases). We have recently determined that loricrin is the major component of CE. We now have isolated and characterized its gene and showed that it has a simple structure with a single intron. We also show that the loricrin gene maps to position 1q21, which, coincidentally, is similar to the location of the profilaggrin and involucrin genes. Human loricrin in 26 kDa and consists of three long glycine-serine-cysteine rich sequence domains that contain quasi-repeating peptides and which form the novel glycine loop motif. These are interspersed by lysine+glutamine rich domains involved in isodipeptide crosslinks. The glycine loops are thought to be involved in organization of epidermal proteins and maintenance of the flexibility of the epidermis. By use of PCR analyses, we have found that human loricrin consists of two allelic size variants, due to sequence variations in the second glycine loop domain only, and these variants segregate in the human population by normal Mendelian mechanisms. Furthermore, there are multiple sequence variants within these two size class alleles due to various deletions of 12 bp (4 amino acids) in the major loop of this glycine loop domain. In order to study the expression and role of TGases in the formation of CE, we have isolated and sequenced cDNA and genomic clones encoding the TGase1 enzyme.(ABSTRACT TRUNCATED AT 250 WORDS)