Intermediate Filament Proteins and Their Associated Diseases

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Abstract
The cytoskeleton consists of three abundant families of fibrillary proteins: microfilaments, microtubules, and intermediate filaments.1,2 Intermediate filament proteins derive their name from their diameter, which is intermediate between the diameters of microfilaments and microtubules.1,2 They differ from actin microfilaments and tubulin microtubules in their large number, their distribution in the cytoplasm and nucleus, their diverse primary structure ( Table 1 ), their nonpolar architecture, their relative insolubility, and their nucleotide-independent dynamics.1-3 The human genome contains at least 65 functional genes encoding intermediate filament proteins, placing them among the 100 largest gene families in humans.4 More than 30 diseases are related to mutations in these genes ( Table 2 ). The majority of them are rare (affecting fewer than 200,000 patients in the United States) or difficult to treat,7 but collectively they affect most tissues, and not all of them are rare, as exemplified by the association of keratin mutations with end-stage liver disease. Intermediate filament proteins have long been considered unique to multicellular eukaryotic organisms,8 in contrast to microfilaments and microtubules, which have prokaryotic ancestors. However, crescentin, which is found in several curved bacteria, including Caulobacter crescentus and Helicobacter pylori, was recently identified as an intermediate filament–like ancestor protein that accounts for the morphologic features of caulobacter.9