Genes for intermediate filament proteins

The increase in specific cell types represents one hallmark of metazoan evolution. It is paralleled by the acquisition of multigene families, which often encode proteins of similar structure but distinct function. One such family is represented by the intermediate filament protein (IF) family. Its members form part of the cytoskeleton of most metazoan cells. Vertebrate IF are organised into five distinct gene families according to sequence identity and expression patterns (Fuchs and Weber, 1994; Herrmann and Aebi, 2000). These include keratins (K), which represent the type I and II homology groups encoded by more than 20 genes, and a further 15 hair keratin genes (Langbein et al., 1999; Rogers et al., 2000), the type III proteins desmin, vimentin, GFAP and peripherin, and the type IV homology group, which encompasses α-internexin, syncoilin (Newey et al., 2001), nestin, synemin and the neurofilament proteins NF-L, -M and -H. The nuclear lamins A/C, B1 and B2 form the type V IF, whereas the eye lens proteins phakinin and filensin constitute a separate group. All 16 known non-keratin IF proteins, including syncoilin (Newey et al., 2001) and synemin (Becker et al., 1995; M. Titeux et al., unpublished), were identified by biochemical, immunological and cDNA cloning methods. The power of the classical approach is best exemplified by the pioneering work of Moll and Franke, who in 1982 established the ‘catalog of human cytokeratins’ (Moll et al., 1982). They laid the groundwork for keratin expression profiles and provided a rational nomenclature. Their data were based on the isolation of keratins from microdissected normal and tumor tissues, as separated in high resolution 2D gels. The numbering system for type II keratins ranges from 1 to 8 with letters for later additions and from 9 to 21 for type I keratins. Hair keratins were named in an analogous way with letters Ha and Hb indicating type I and II hair keratins, respectively (Langbein et et al., 1999; Rogers et al., 2000). Subsequent work established that all IF proteins, with the exception of a few polymorphic variants (Mischke and Wild, 1987; Korge et al., 1992), are encoded by single copy genes (Fuchs and Weber, 1994). One difficulty of the classical biochemical and genetic approach is that potential minor keratins and other IF proteins, present in only a few cells of a tissue, or expressed transiently during embryonic development, may have escaped detection. Gene mapping studies revealed that genes coding for nonkeratin IF proteins are not clustered (International Human Genome Sequencing Consortium, 2001). All type I keratin genes (except K18; Waseem et al., 1990) are clustered on chromosome 17q21 and type II genes on 12q13 (International 2569