Abstract
Both epidermal keratinocytes and hair follicle trichocytes of the hair-forming compartment are cell types whose characteristic keratin intermediate filaments (KIF) are not only vital as long as these cells are alive but also of fundamental importance once they have undergone their programed suicide maturation pathway. In the epidermis, this scenario leads to the formation of a protective surface layer of corneocytes, the stratum corneum, in the hair follicle to the production of hair, a unique mammalian acquisition, which, besides generating a mechanical safeguard, provides thermal insulation, sensory capacities, and camouflage (in humans these properties have been largely lost during evolution). In both cases, the KIF fulfill their biological function in a concerted action with so-called keratin-associated proteins (KAPs). These proteins can be divided into those that are either associated with epithelial keratins (examples of these are loricrin, involucrin, repetin, and the SPRR and S100 families of proteins) or with hair keratins (for a review, seePowell and Rogers, 1997). The hair KAPs were originally identified as being the major part of the amorphous mass surrounding the 10 nm hair KIF in the cortex of the hair follicle. At present, KAP amino acid composition, protein modeling, and recent electron microscopic observations have led to the hypothesis that KAPs play a role in the lateral linkage in/between the hair KIF, perhaps being the glue that holds the hair fiber together. In addition, more than 30 years of hair follicle protein studies, mainly performed in sheep, mouse, rabbit, but more recently, also in humans, have shown that an amazingly large number of KAP proteins exists. Based on their main amino acid composition, these proteins have been previously divided into three categories: the high sulfur (HS) ( 30 mol%), and high glycine–tyrosine (HGT)-KAPs. In recent years, extensive bioinformatic analysis has resulted in the identification of what is probably the complete number of human KAP genes (Rogers et al, 2001, 2002, 2004; Shibuya et al, 2004; Yahagi et al, 2004), which could be subdivided into 21 KAP gene families (23 when other species are included) (Table I). KAP genes are small in size (approximately 1 kb), consist generally of only one exon, and are grouped together in five domains on the human chromosomes 17q21.2, 21q22.1, 21q22.3, 11p15.5, and 11q13.4 (Table I). Concomitant with the identification of the 85 gene loci found on these domains, transcriptional expression via cDNA isolation/characterization, RT-PCR analysis, and in situ hybridization has now provided a fairly clear picture about whether, and where, the majority of KAP proteins are expressed in the hair follicle, that being predominantly in the differentiated portions of the hair cortex and cuticle, with a few KAP members showing expression either in only half of the cortex or concomitant expression in the hair matrix region (Rogers et al, 2001, 2002, 2004; Shimomura et al, 2002a,b,2003; Shibuya et al, 2004; Yahagi et al, 2004, see also Table I). Compared with the extensive amount of work on human KAPs performed at the genomic and transcriptional level, very little has been carried out regarding the demonstration of human KAP proteins, largely because of their small size and difficulties associated with the generation of KAP-specific antibodies, although a pan-antibody recognizing the KAP1 family members exists (Shimomura et al, 2002b).
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