Intermediate filaments families

The nuclear envelope is a supramolecular assembly that lines the inner surface of the nucleus. The major proteins of the envelope are the A, B, and C lamins, and it has been suggested that they may be members of the intermediate filament family. What characteristic features should the lamins possess for this to be so ... 

Vimentin is a 57-kD protein that was initially isolated from a mouse fibroblast culture7>" Its name derives from the Latin vimentum, describing an array of flexible rods. This IFP is considered to be the primordial member of the intermediate filament family, because it is present in most, if not all, fetal cells early in development. Moreover, when two or more IFPs are coexpressed by a cell line or neoplasm, vimentin is virtually always one of them." Accordingly, vimentin is not considered to be cell type-specific. From the perspective of mesenchymal tumor pathology, it is of interest that vimentin shows... 

Cytokeratins are members of the intermediate filament class of cytoskeletal proteins. Cytokeratins are a large protein family comprising two subfamilies of polypeptides, i.e. acidic (type I) and basic (type II) ones. Cytokeratin form tetramers, consisting of two type I and two type II polypeptides arranged in pairs of laterally aligned coiled coils. The distribution of the different type I and II cytokeratins in normal epithelia and in carcinomas is differentiation-related and can be used for cell typing and identification. 

Neurofilaments belong to the family of intermediate filaments and usually are found in association with neurotubules. The function of these two organelles has been... 

The components of the intermediate filaments belong to five related protein families. They are specific for particular cell types. Typical representatives include the cytokeratins, desmin, vimentin, glial fibrillary acidic protein (GFAP), and neurofilament. These proteins all have a rod-shaped basic structure in the center, which is known as a superhelix ( coiled coil see keratin, p. 70). The dimers are arranged in an antiparallel fashion to form tet-ramers. A staggered head-to-head arrangement produces protofilaments. Eight protofilaments ultimately form an intermediary filament. 

Riemer, D., Karabinos, A., and Weber, K. (1998). Analysis of eight cDNAs and six genes for intermediate filament (IF) proteins in the Cephalochordate Branchiostoma reveals differences in the IF multigene families of lower chordates and the vertebrates. Gene 211, 361-373. 

Fig. 3. A comparison of cell-cell and cell-substrated anchoring junctions. (A) Desmosomes anchor keratin filaments through desmoplakin. One half of a desmosome, which is an intercellular junction that anchors intermediate filaments (IFs) to the plasma membrane, is shown. The transmembrane desmosomal cadherins, desmogleins (Dsg) and desmocollins (Dsc), mediate adhesion through their extracellular domains, and associate with plakophilins (Pkp) and plakoglobin (Pg) through their cytoplasmic domains. These proteins in turn interact with the N-terminus of the plakin family member desmoplakin, which anchors IF to the junction through its G-terminus. (B) Endothelial VE-cadherin-based junctions anchor vimentin through...

Green, K. J., Virata, M. L. A., Elgart, G. W., Stanley, J. R., and Parry, D. A. D. (1992b). Comparative structural analysis of desmoplakin, bullous pemphigoid antigen and plectin Members of a new gene family involved in organization of intermediate filaments. Int. J. Biol. Macromol. 14, 145—153. 

Together with actin microfilaments and microtubules, keratin filaments make up the cytoskeleton of vertebrate epithelial cells. Keratins belong to a family of intermediate filament proteins that form a-helical coiled-coil dimers that associate laterally and end to end to form 10 nm diameter filaments. Keratin and actin filaments and microtubules form an integrated cytoskeleton that preserves the shape and structural integrity of the ker-atinocyte as well as serves to transmit mechanical loads. Keratins account for about 30% of the total protein in basal cells. 

A stressed cell undergoes precise biochemical and morphological changes. General protein synthesis is switched off and a set of specific mRNAs are translated to produce the stress proteins. The intermediate filaments of the cytoskeleton become perinuclear and heat-shock proteins of the 70kDa family are translocated into the nucleus. The 70kDa family appears to play a role in differentiation and development and is crucial to the survival of stressed... 

Cytokeratin belongs to a family of intermediate filament proteins in epithelial cells. 

The keratin family of proteins comprises two of the six classes of intermediate filament proteins found in the cytosol of eukaryotic cells. They provide the intracellular structural stability that complements the intercellular mechanical cohesion provided by desmosomes. Keratin filaments cross the entire cytosol of keratinocytes and their ends are tightly attached to desmosomes by desmoplakin (Fig. 5.9) or, in basal cells, to the related plakin (BP230) and plectin proteins in hemidesmosomes. 

Five classes of intermediate filament proteins have been described, generally referred to as types I through V. Types I and II are the acidic and basic polypeptides, respectively, which comprise the keratins and cytokeratins, a family of heteropolymers that are abundant in epithelia. Type III consist of vimentin, desmin, glial fibrillary acidic protein, and peripherin. Of these, desmin has specific importance... 

C -Keratin, which is the primary component of wool and hair, consists of two right-handed o helices intertwined to form a type of left-handed superhelix called an a coiled coil, ot-Keratin is a member of a superfamily of proteins referred to as coiled-coil proteins (Figure 2,43). In these proteins, two or more a helices can entwine to form a verv stable structure, which can have a length of 1000 A (100 nm, or 0.1 jiim) or more. There are approximately 60 members of this family in humans, including intermediate filaments, proteins that contribute to the cell cytoskeleton (internal scaffolding in a cell), and the muscle proteins myosin and tropomyosin (Section 34.2). Members of this family are characterized by a central region of 300 amino acids that contains imperfect repeats ol a sequence of seven amino acids called a heptad repeal. 

Anderton BH. Intermediate filaments A family of homologous structures. / Mmsc/c Res Cell Motil. 1981 2 141-166. 

The soft epithelial keratin intermediate filaments comprise approximately 20 different keratin polypeptides. " The polypeptides, numbered 1 through 20, comprise type II (basic) keratins and type I (acidic) keratins (Table 8.2). This family of intermediate filaments is crucial in diagnostic IHC for the identification of carcinomatous differentiation and for identification of specific carcinoma subtypes. 

Vimentin is a 58-kD intermediate filament found predominantly in mesenchymal cells. However, vimentin is expressed in most spindle cell carcinomas and is reported by some to be expressed in a relatively high percentage of pulmonary adenocarcinomas. Thyroid transcription factor-1 (TTF-1), a 38- to 40-kD transcription factor member of the NKx2 family of home-odomain transcription factors, is expressed in thyroid and pulmonary epithelial cells. 49 TTF-1 binds to and activates the promoters for Clara cell secretory protein and surfactant proteins A, B, and As reported... 

Cytokeratins (CKs) are a family of intracytoplasmic intermediate filament proteins present in almost all epithelia. Expression of each CK molecule depends on cell type and differentiation status, and therefore specific CKs can be used as markers to identify particular types of epithelial tumors (Table 16.5). CK7 is found in a wide variety of epithelia including the columnar and glandular epithelium of the lung, cervix, and breast, as well as in the bile duct, collecting ducts of the kidney, urothelium, and mesothelium, but not in most gastrointestinal epithelium, hepatocytes, proximal and distal tubules of the kidney, and squamous epithelium. In contrast, CK20 shows relatively restricted expression and is present in gastrointestinal epithelium, Merkel cells of the epidermis, and urothelium. 

Each type of cytoskeletal filament is a polymer of protein subunits (Table 5-4). Monomeric actin subunits assemble into mlcrofllaments dimeric subunits composed of a- and p-tubulin polymerize into microtubules. Unlike mlcrofllaments and microtubules, which are assembled from one or two proteins, intermediate filaments are assembled from a large diverse family of proteins. The most common intermediate filaments, found in the nucleus, are composed of lamins. Intermediate filaments constructed from other proteins are expressed preferentially in certain tissues for example, keratin-containing filaments in epithelial cells, desmin-contalnlng filaments In muscle cells, and vimentin containing filaments In mesenchymal cells. 

A FIGURE 6-8 Desmosomes. (a) Schematic model showing components of a desmosome between epithelial cells and attachments to the sides of keratin intermediate filaments, which crisscross the interior of cells. The transmembrane CAMs, desmoglein and desmocollin, belong to the cadherin family. 

Several different gene families encode the various proteins that make up the cytoskeleton. These proteins are present in varying amounts In almost all cells. In vertebrates, the major cytoskeletal proteins are the actins, tubulins, and intermediate filament proteins like the keratins. We examined the origin of one such family, the tubulin... 

One family of IFAPs, the plakins, is responsible for linking IFs with both microtubules and mlcrofllaments. One plakln family member is plectin, a 500,000-MW protein that has been shown to cross-link intermediate filaments with microtubules and actln filaments in vitro. Plectin also Interacts with other cytoskeletal proteins, including spectrin, microtubule-associated proteins, and lamin B. Immunoelectron microscopy reveals gold-labeled antibodies to plectin decorating short, thin connections between microtubules and vimentin. 

Intermediate filaments are a family of structures intermediate in size between the thin actin filaments and the fat microtubules. Intermediate filaments are formed by coiled-coil interactions between intermediate filament proteins. 

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