Intermediate filaments is actually a generic name for a family of proteins grouped into 6 classes based on sequence and biochemical structure that serve similar functions in protecting and shaping the cell or its components. Cytoskeleton structure, dynamics, function and disease 244 long. These modifications and protein associations contribute in key ways to the function and dynamics of intermediate filaments. Cytoskeleton structure, dynamics, function and disease. A major function shared by several types of cytoplasmic intermediate filaments ifs is to stabilize cellular architecture against the mechanical forces it is subjected to. Type iii intermediate filaments contain three domains, named the head, rod and tail domains. A novel role for stabilization by disulfide bonding he wang a laboratory of skin biology, national institute of arthritis and musculoskeletal and skin diseases, national institutes of health, bethesda, maryland 20892. Microfilaments are made of actin and are crucial for muscle. The ins and outs of intermediate filament organization. The filaments were named intermediate, because their 10nm diameters are intermediate between those of the thick and thin filaments in striated muscles, where they. This book provides new insights into the structure functional features, dynamics, and cytoskeletons relationship to diseases. As for other fibrous cytoskeletal arrays, a crucial determinant of this function is the spatial organization of ifs in the cytoplasm.
Chicago avenue, chicago il 60611, usa intermediate. Toward unraveling the complexity of simple epithelial keratins in human disease m. Intermediate in size between actin and microtubules flexible, ropelike polymers give cells mechanical strength in epithelia, there are ropes of intermediate filaments throughout the cytoplasm there are contacts between the cells where filaments are sutured together provide entire tissue with mechanical strength skin. They are ubiquitous constituents of the structural scaffold of the eukaryotic cells and considered mechanical integrators of cytomatrix 2.
Molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds harald herrmann and ueli aebi. Individual filament structure and function wikilectures. These filaments, which extend throughout the cytoplasm and inner nuclear membrane are composed from a large family of proteins that can be broadly grouped into five classes. Mitochondrial location and function depend on intact ifs, as demonstrated for desmin, keratins and neurofilaments. A ll mammalian cells contain a complex cytoskeleton composed of three principal structural proteins and.
A 11 mammalian cells contain a complex cytoskeleton. Molecular structure, assembly mechanism, and integration into functionally distinct intracellular scaffolds. The availability of a structural model of ifs could also be the key to understanding the mechanisms of if related genetic diseases, where structural flaws that originate at the genetic or molecular level may cause major. Introduction intermediate filaments ifs represent one of the main cytoskeletal. The primary function of intermediate filaments is to create cell cohesion and prevent the acute fracture of epithelial cell sheets under tension. Steinert skin biology branch, national institute of arthritis and musculoskeletal and skin diseases, national institutes of health, bethesda, liaryland, u. This rod domain coils around that of another filament to form a dimer, with the nterminal and cterminal of each filament aligned. Intermediate filament if proteins belong to a large and diverse gene family with broad representation in vertebrate tissues.
This is made possible by extensive interactions between the constituent protofilaments of an intermediate filament, which enhance its resistance to compression, twisting, stretching and bending forces. Intermediate filaments are cytoskeletal proteins with a diameter intermediate between the thin and thick myofibrils, measuring between 10 and 12 nm in diameter. An intermediate filament is categorized based on its amino acids and protein structure. In vitro assembly and structure of trichocyte keratin. Sitespecific glycosylation regulates the form and function. Structure, function, and dynamics of keratin intermediate.
The apparent diameter was reported to be in the range of 10 nm and, therefore, intermediate between that of actin filaments 6 nm and myosin filaments 15 nm. Intermediate filaments are also made up of numerous. Cytoplasmic intermediate filaments revealed as dynamic and. A structural scaffolding of intermediate filaments in. This criterion was then used to investigate other tissues, as well as cultured cells, for the presence of 10nmtype filaments goldman 1971. However, very few crossbridging proteins are specific for ifs most ifassociated. Cytoskeleton filaments, structure and functions earth.
The structure of proteins that form intermediate filaments if was first predicted by computerized analysis of the amino acid sequence of a human epidermal keratin derived from cloned cdnas. The ifs are a large protein family with more than 70 members. In contrast to the latter, ifs constitute a network that extends from the nuclear envelope throughout the cytoplasm, and in many cases, interact with cell surface domains. Although considered the toughest cytoskeletal fibers, studies in cultured cells have revealed that if can be surprisingly dynamic and highly regulated. The cytoskeleton microtubules microfilaments intermediate filaments also motor proteins and other associated proteins that integrate system functions of the cytoskeleton, fig 9. Laminopathies and the long strange trip from basic cell biology to therapy howard j. The cytoskeleton is a highly dynamic intracellular platform constituted by a threedimensional network of proteins responsible for key cellular roles as structure and shape, cell growth and development, and offering to the cell with motility that being the ability of. The cardiomyopathy and lens cataract mutation in alpha bcrystallin alters its protein structure, chaperone activity and interaction with intermediate filaments in vitro. The function of intermediate filaments is largely mechanical, meaning they provide support for the cell so that other microfilaments can more readily do their transport jobs. Intermediate filament if constitutes an important cytoskeletal component in nearly all the vertebrate cells. Although intermediate filaments ifs as one of the major components of the eukaryotic cytoskeleton are widely spread in nature and have been known for more than a quarter of a century, their. The availability of a structural model of ifs could also be the key to understanding the mechanisms of if. Dec 25, 2000 in vitro assembly and structure of trichocyte keratin intermediate filaments. Structure, function, and dynamics of keratin nternlediate filaments peter m.
Intermediate filaments were discovered in eukaryotic cells in the late 1960s, and their name comes from the fact that their diameter is intermediate between mfs and mts. Nucleoskeleton dynamics and functions in health and disease peter meinke, alexandr a makarov, phu le thanh, daina sadurska, eric c schirmerwellcome trust centre for cell biology and institute of cell biology, university of edinburgh, edinburgh, ukabstract. The investigation of cultured cells and of tissues from various developmental stages has furnished a host of information on the interand intracellular distribution of the different types of intermediate filaments and led to the contention that they have a structural and organizing function. Intermediate filaments definition of intermediate filaments. This traditional function is now augmented by organellerelated and proteintargeting roles. Intermediate filaments are composed of a family of related proteins sharing common structural and sequence features. Intermediate filaments are cytoskeletal polymers encoded by a large family of differentially expressed genes that provide crucial structural support in the cytoplasm and nucleus of higher eukaryotes. Structure, dynamics, function and disease fuchs, e.
Intermediate filaments as a target of signaling mechanisms. Intermediate filaments, like keratin, support the cell structure and help cushion mechanical stress in areas such as the skin. Structure and assembly article pdf available in cold spring harbor perspectives in biology 811. Sorry, we are unable to provide the full text but you may find it at the following locations.
Apoptosis and keratin intermediate filaments cell death. Review structure, function, and dynamics of keratin intermediate filaments peter m. Steinert, skin biology branch, national institute of arthritis and musculoskeletal and skin diseases, national institutes of health, bethesda, maryland, u. Steinert skin biology branch, national institute of arthritis and musculoskeletal and skin diseases, national institutes of health, bethesda, maryland, u. Intermediate filaments are also made up of numerous different protein subunits called keratin and 70. However, many disease conditions seem to link to the nonmechanical functions of ifs, many of which have been defined only in the past few years.
Intermediate filament proteins and their associated diseases. Analysis of a second keratin sequence revealed that the two types of keratins share only about 30% amino acid sequence homology but share similar patterns of secondary structure domains. Intermediate filament proteins ifs maintain cell and tissue integrity, based on evidence of their polymerization and mechanical properties, abundance and disease associated phenotypes. Structure, dynamics, function and disease intermediate filaments. In this disease mutations in the keratin genes interfere with the formation of keratin filaments in the epidermis, due to which the skin is highly vulnerable to mechanical injury, and even a gentle pressure can rupture its. Mar 07, 2018 thank you for submitting your article sitespecific glycosylation regulates the form and function of the intermediate filament cytoskeleton for consideration by elife. Ifs are present both in the cytoplasm and in the nucleus. Notably, intermediate filament chains possess a characteristic central.
In fact, many types of if are now known to engage in a remarkable array of movements that are closely associated with their assembly, disassembly and. Dysfunctions of neuronal and glial intermediate filaments in disease. The cytoplasm of animal cells is structured by a scaffolding composed of actin microfilaments, microtubules, and intermediate filaments. The role of vimentin intermediate filaments in the. Intermediate filaments are the structures that form a network around the nucleus and encompass the periphery of the cell. With unique assemblydisassembly dynamics and physical properties, cytoplasmic intermediate filaments play an important role in regulating cell shape.
Eriksson, 1,2 thomas dechat, 3 boris grin, 3 brian helfand, 4 melissa mendez, 3 hannamari pallari, 1,2,5 and robert d. Intermediate filaments are seen in cells of ectodermal, mesodermal, and endodermal derivation. Interestingly, they can even be found inside the nucleus. The cytoskeleton is a highly dynamic intracellular platform constituted by a threedimensional network of proteins responsible for key cellular roles as structure and shape, cell growth and development, and offering to the cell with motility that being the ability of the entire cell to move and for material to be moved within the cell in a regulated fashion vesicle trafficking. Transgenic mice expressing a mutant keratin 10 gene reveal the likely genetic basis for epidermolytic hyperkeratosis. Structure and dynamics of human vimentin intermediate. Structure, function, and dynamics of keratin intermediate filaments. Making heads and tails of intermediate filament assembly, dynamics and networks. Structural features of keratin intermediate filaments journal of investigative dermatology 1994, 103 s5, 19s24s.
The rare human genetic disease epidermolysis bullosa simplex illustrates the importance of the intermediate filaments. Keratins and disease at function, revealing the potential. The specific dna sequence for the rod domain may differ between different type iii intermediate filaments, but the structure of the protein is highly conserved. Green department of pathology, northwestern university feinberg school of medicine, 303 e. In vitro assembly and structure of trichocyte keratin intermediate filaments. Microfilaments as a part of the cytoskeleton keep organelles in place within the cell. Intermediate filaments colloquium series on building blocks.
Vimentin if proteins have been implicated in many aspects of cancer initiation and progression, including tumorigenesis, epithelialtomesenchymal transition, and the metastatic spread of cancer. Intermediate filaments, so named because their 10nanometer diameter is intermediate between that of microfilaments 6 nanometers and microtubules 23 nanometers, assemble into an anastomosed network within the cytoplasm. Intermediate filaments are part of the cytoskeleton and nucleoskeleton. The intermediate filaments are formed by ropelike polymers, which are composed of fibrous proteins. Intermediate filaments are a primary component of the cytoskeleton, although they are not found in all eukaryotes, and are absent in fungi and plants 1.
Some intermediate filaments are even arranged in a meshlike pattern to provide for the different support needs of different kinds of cells. These filaments are composed of many different but homologous proteins. Initially designated intermediate because their average diameter 10 nm is between those of narrower microfilaments actin and wider myosin filaments found in muscle cells, the diameter of intermediate filaments is now commonly compared to actin microfilaments 7 nm and. Microfilaments definition, structure, functions and diagram. Chemical crosslinking indicates a staggered and antiparallel protofilament of desmin intermediate filaments and characterizes one higherlevel complex between protofilaments. The 40 or more known intermediate filament proteins have been classified into five types. Pdf proteins of the intermediate filament if supergene family are ubiquitous structural components that comprise, in a cell typespecific manner. Pdf intermediate filaments as a target of signaling. They play an important role in providing mechanical strength of the cell and tissue, growth and regeneration, cell survival and apoptosis, and finally cell migration.
Models to study intermediate filament dynamics and functions. A chemically heterogeneous, developmentally regulated class of proteins. Eisenmann cell structure and function flashcards quizlet. Intermediate filament an overview sciencedirect topics. Introduc tion although it is only relatively recently that intermediate filaments ifs have been recognized as a superfamily of l onm fibers ubiquitous in multicellular eukaryotes, their existence has been known for. Intermediate filaments are dynamic and motile elements of. Mechanically induced signal transduction has an essential role in development. Ranging in size from 8 to 12 nanometers in diameter. Describe the nuclear pore 80100nm, composed of 3 rings. Frontiers intermediate filaments at the junction of. Desmin, vimentin, nestin, lamin, and plectin are intermediate filaments expressed in muscle.
Intermediate filaments are a very broad class of fibrous proteins that play an important role as both structural and functional elements of the cytoskeleton. They can depolymerize disassemble and reform quickly, thus enabling a cell to change its shape and move. Structure, function, and dynamics of keratin intermediate filaments peter m. Nucleoskeleton dynamics and functions in health and disease. The 40 or more known intermediate filament proteins have been classified into five types which show very specific rules of expression in specialized cell types, and include. The disease is caused by mutation in gene encoding lamin a intermediate filament protein that comprises part of nuclear lamina of nuclear envelope. The clinical manifestations of abnormal intermediate filament proteins can be due to mutations with high penetrance, such as those that cause epidermolysis bullosa simplex 2,11,12,38,41.
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