Intermediate filaments (IFs) are one of the three major components of the cytoskeleton in eukaryotic cells, along with microtubules and actin filaments. Intermediate filament proteins are a diverse family of fibrous proteins that assemble into intermediate filaments, which are 10-12 nanometers in diameter. These filaments provide mechanical strength, stability, and resilience to cells, helping them maintain their shape and resist mechanical stress.
Intermediate filament proteins are classified into six major types based on their sequence homology, structure, and function:
- Type I and II: Acidic and basic keratins, respectively, are found primarily in epithelial cells and form the cytoskeleton of these cells. They also constitute the main structural proteins in hair, nails, and the outer layer of the skin.
- Type III: This group includes vimentin, desmin, peripherin, and glial fibrillary acidic protein (GFAP). Vimentin is widely expressed in mesenchymal cells, while desmin is found in muscle cells, peripherin in neurons, and GFAP in glial cells. Each of these proteins has tissue-specific functions and contributes to the mechanical properties of the respective cells.
- Type IV: Neurofilament proteins (NF-L, NF-M, and NF-H) are specific to neurons and form the main cytoskeletal component of axons, providing structural support and regulating axonal diameter.
- Type V: Nuclear lamins (lamins A, B, and C) are intermediate filament proteins that form a mesh-like structure, called the nuclear lamina, beneath the inner nuclear membrane. Lamins provide mechanical support to the nucleus and are involved in various nuclear functions, such as DNA replication, transcription, and chromatin organization.
- Type VI: Nestin is a type VI intermediate filament protein expressed primarily in neural stem cells and some progenitor cells during development. Its expression is downregulated as cells differentiate, and it is replaced by other intermediate filament proteins specific to mature cell types.
Mutations or defects in intermediate filament proteins can lead to various diseases and disorders, known as intermediate filamentopathies. These include epidermolysis bullosa simplex (caused by keratin mutations), desmin-related myopathies (caused by desmin mutations), and several forms of muscular dystrophy and neuropathies (caused by mutations in nuclear lamins and neurofilament proteins).