The Catalog of Human Hair Keratins

Abstract

The human type II hair keratin subfamily consists of six individual members and can be divided into two groups. The group A members hHb1, hHb3, and hHb6 are structurally related, whereas group C members hHb2, hHb4, and hHb5 are rather distinct. Specific antisera against the individual hair keratins were used to establish the two-dimensional catalog of human type II hair keratins. In this catalog, hHb5 showed up as a series of isoelectric variants, well separated from a lower, more acidic, and complex protein streak containing isoelectric variants of hair keratins hHb1, hHb2, hHb3, and hHb6. Both in situ hybridization and immunohistochemistry on anagen hair follicles showed that hHb5 and hHb2 defined early stages of hair differentiation in the matrix (hHb5) and cuticle (hHb5 and hHb2), respectively. Although cuticular differentiation proceeded without the expression of further type II hair keratins, cortex cells simultaneously expressed hHb1, hHb3, and hHb6 at an advanced stage of differentiation. In contrast, hHb4, which is undetectable in hair follicle extracts and sections, could be identified as the largest and most alkaline member of this subfamily in cytoskeletal extracts of dorsal tongue. This hair keratin was localized in the posterior compartment of the tongue filiform papillae. Comparative analysis of type II with the previously published type I hair keratin expression profiles suggested specific, but more likely, random keratin-pairing principles during trichocyte differentiation. Finally, by combining the previously published type I hair keratin catalog with the type II hair keratin catalog and integrating both into the existing catalog of human epithelial keratins, we present a two-dimensional compilation of the presently known human keratins.The large keratin multigene family comprises the epithelial keratins (also designated as "cytokeratins" or historically "soft keratins"), which are differentially expressed in the various types of epithelia, and the hair keratins (historically designated as "hard keratins"), which are involved in the formation of hard keratinized structures such as hairs, nails, claws, etc. These keratins can be divided into acidic type I and basicto-neutral type II members, which form the 10-nm intermediate filament network of the cytoskeleton of epithelial cells through the obligatory association of equimolar amounts of type I and type II keratins (for review see Refs. 1-3).Earlier gel electrophoretic studies on native hair keratins of several mammals including man revealed the presence of four type I (44 -48 kDa) and four type II (55-60 kDa) members (4, 5). According to a proposal by Heid et al. (4), hair keratins were collectively designated "H" for hair, "b" for the basic members (Hb), 1 and "a" for the acidic members (Ha), with the two-dimensionally resolved and Coomassie-stained protein spots of each subfamily being numbered from 1 to 4 in a counterclockwise manner. In addition to the "major" hair keratins hHa1-hHa4 and hHb1-hHb4, a weakly expressed additional pair was de...

HOXC13 Is Involved in the Regulation of Human Hair Keratin Gene Expression

“…In beard hairs, cells in the lowermost portion of the central medulla also contained HOXC13 protein in their nuclei. Accordingly, we generated ␤-galactosidase reporter gene constructs with promoter fragments of type I hair keratin genes hHa2, hHa5, and hHaA, which are expressed in these regions (13,15,16), for cotransfection studies with a HOXC13 expression vector. These studies clearly showed that hair keratin promoters strongly activated the reporter gene in the presence of functional but not homeobox deleted HOXC13.…”

“…IIF on cryostat sections of plucked beard hair follicles and human scalp sections was carried out as described previously (13,15). The HOXC13 antiserum was generated using the synthetic oligopeptide PEPSGALPDGDDLS-C as antigen.…”

“…In Situ Hybridization and Indirect Immunofluorescence-ISH 1 was carried out on cryostat sections of human scalp (kindly provided by Dr. Bernard Cribier, Strasbourg, France) as previously described in detail (13,15). HOXC13 transcripts were detected using a specific PCR fragment that encompassed ϳ300 bp of the 3Ј-untranslated regions of the human HOXC13 mRNA (17).…”

“…In the past years, our laboratory has elucidated the organization of the human type I and type II hair keratin gene loci and characterized the sequential expression of their members during trichocyte differentiation (12)(13)(14)(15) Based on this knowledge, we selected three human type I hair keratin genes hHa5, hHa2, and hHa7 as well as the transcribed pseudogene hHaA, whose mRNA expression patterns in the lower hair forming compartment of the human hair follicle (13,16) corresponded to that described for Hoxc13 in mouse hair follicles (6), and investigated whether they are target genes for HOXC13. In the present study, we provide strong evidence that these hair keratin genes are transcriptionally up-regulated by HOXC13 primarily via binding of the transcription factor to distinct core recognition motifs, TAAT and TTAT, in the respective proximal promoters.…”

Characterization of a First Domain of Human High Glycine-Tyrosine and High Sulfur Keratin-associated Protein (KAP) Genes on Chromosome 21q22.1

“…Hair keratins, a subset of the large keratin family whose members are found in all cells of epithelial origin (3,4), represent two multigene families, the type I (acidic) and type II (basic) families that comprise 15 members in humans (5,6). They form the 8 -10-nm intermediate filaments of trichocytes by co-polymerization of type I and type II members, which are differentially expressed during hair fiber development (7,8). KAPs, which form the matrix between the hair keratin intermediate filament bundles through extensive disulfide bond cross-linking with cysteine residues in the head and tail domains of hair keratins, possess either high cysteine or high glycine-tyrosine content (2) and are further divided into three broad groups containing, to date 17 families.…”