Cytoskeleton III: Intermediate Filaments

Cytoskeleton III:
Intermediate Filaments The final group of filamentous proteins--the intermediate filaments--is quite diverse but they are all polymers of fibrous protein monomers that are members of a large family of structurally and genetically related proteins. Among the members of this family are vimentins, neurofilament proteins, keratins (an epithelial cell protein which is also the protein in hair and nails), and lamin, a protein that is crucial to maintaining the integrity of the nuclear membrane. As their name intermediate filament implies they have a typical diameter (about 10 nm) that is larger than actin filaments (8nm) and smaller than microtubules (25 nm); that is, they were the last filament to be discovered and had a size in between the first two.
There are two basic distinctions between intermediate filaments and the other cytoskeletal elements-- actin filaments and microtubules. First, no one has ever found substances that use intermediate filaments that help in movement. That is, unlike myosins for actin filaments, or kinesins and dyneins for microtubules, there are no known motor proteins that move things along intermediate filaments. Therefore, they are thought to be only structural. Second, the intermediate filaments are more stable than either actin filaments and microtubules. That are permanently stable, because they can disassemble during cell division, for example, but in a non-dividing cell they're thought to be pretty stable. That's probably because the proteins that make up intermediate filaments are different in structure from actin or tubulin--they're long, thin protein rods, not round protein balls.
Intermediate filaments are grouped into about half a dozen different classes depending on their general structure and relatedness to each other. Probably the most abundant intermediate filament proteins in animals are the keratins, which are common in epithelial tissue like skin and gut, and which make up hair, nails, animal fur, etc. However, the intermediate filament protein found in the most different kinds of cells are the vimentins. Whatever, the kind of protein that makes it up, most intermediate filaments have the same general structure. Two long monomers of IF protein, which each contain extensive alpha helical regions, wrap around each other in a "coiled coil" structure (Fig. 19-51 of Lodish et al.). This dimer then lines up more or less side by side with another pair of IF proteins, but in opposite directions (as determined by the N and C termini of the protein). Then these "antiparallel tetramers" stack end to end to form a long protofilament. The protofilaments first dimerize into "protofibrils" and then these form tetramers wrapped around each other to make real intermediate filaments. If you do the computation you see that each IF monomer dimerizes then dimerizes a second time to give the antiparallel tetramer (which has four monomers), which polymerizes lengthwise into a protofilament (still 4 monomers in diameter), which dimerizes (8 monomers) into a protofibril which tetramerizes (32 monomers) into an intermediate filament. Not surprisingly, intermediate filaments are pretty rigid and strong as a result. The function of intermediate filament proteins thus seems to be to add tensile strength to cells.
Intermediate filaments are also important in forming tissues (that is, in tying cells together), especially the sheets of epithelial tissue that make up skin and the lining of the digestive tract, which are subjected to constant stress and stretching, and as the book points out, there are some human skin diseases that are caused by mutations in IF proteins, especially keratins. This demonstrates the essential function of these proteins in maintaining the integrity of the skin. IF proteins are also important in linking the cytoskeleton to membranes and thereby giving shape and strength to cells or to organelles (like the nucleus where nuclear lamins attach to the nuclear membrane and apparently help maintain the structure of the nucleus.)
That said, far less is known about intermediate filaments and the other proteins that interact with them than is know about the other cytoskeletal elements. In part that is because the IFs were discovered later than the other parts of the cytoskeleton. For example, actin filaments have been studied for decades because of their role in muscle contraction and thus there's been considerable interest in understanding the interaction of actin and myosins. And partly, the fact that IFs are structural and not involved in movement is regarded by some people as less interesting than their more active cousins the microtubules and actin filaments. That's likely to change as we learn more about what they do and discover other diseases that are traceable to malfunctions of intermediate filament proteins.