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Intermediate Filament

 
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Intermediate filaments (IFs) are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of actin
Actin

Actin is a Globular_protein, roughly 42-kDa protein found in all Eukaryote where it may be present at concentrations of over 100 ?M. It is also one of the most highly-Conservation proteins, differing by no more than 20% in species as diverse as algae and humans....
 (microfilament
Microfilament

Microfilaments are the thinnest filaments of the cytoskeleton found in the cytoplasm of all eukaryotic cell . These linear biopolymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces....
s) and microtubule
Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s, although they were initially designated 'intermediate' because their average diameter was between those of narrower microtubule
Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s and wider myosin
Myosin

Myosins are a large family of motor proteins found in eukaryotic Biological tissue. They are responsible for actin-based motility.Following the discovery, by Pollard and Korn, of enzymes with myosin-like function in Acanthamoeba, a large number of divergent myosin genes have been discovered throughout eukaryotes....
 filaments. Most types of intermediate filaments are cytoplasm
Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
ic, but one type, the lamins, are nuclear.

domain structure of IF molecules is conserved.






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Intermediate filaments (IFs) are a family of related proteins that share common structural and sequence features. Intermediate filaments have an average diameter of 10 nanometers, which is between that of actin
Actin

Actin is a Globular_protein, roughly 42-kDa protein found in all Eukaryote where it may be present at concentrations of over 100 ?M. It is also one of the most highly-Conservation proteins, differing by no more than 20% in species as diverse as algae and humans....
 (microfilament
Microfilament

Microfilaments are the thinnest filaments of the cytoskeleton found in the cytoplasm of all eukaryotic cell . These linear biopolymers of actin subunits are flexible and relatively strong, resisting buckling by multi-piconewton compressive forces and filament fracture by nanonewton tensile forces....
s) and microtubule
Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s, although they were initially designated 'intermediate' because their average diameter was between those of narrower microtubule
Microtubule

Microtubules are one of the components of the cytoskeleton. They have a diameter of 25 Nanometre and length varying from 200 nanometers to 25 micrometers....
s and wider myosin
Myosin

Myosins are a large family of motor proteins found in eukaryotic Biological tissue. They are responsible for actin-based motility.Following the discovery, by Pollard and Korn, of enzymes with myosin-like function in Acanthamoeba, a large number of divergent myosin genes have been discovered throughout eukaryotes....
 filaments. Most types of intermediate filaments are cytoplasm
Cytoplasm

The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
ic, but one type, the lamins, are nuclear.

Structure

The domain structure of IF molecules is conserved. Each protein has a non-alpha-helical (globular) domain at the N and C-termini which surrounds the alpha-helical rod domain. The basic building block for IFs is a parallel and in register dimer
Dimer

File:Carboxylic acid dimers.pngA dimer is a chemical or biological entity consisting of two identical subunits called monomers, which are held together by either intramolecular forces or weaker intermolecular forces....
. The dimer is formed through the interaction of the rod domain to form a coiled coil
Coiled coil

A coiled coil is a structural motif in proteins, in which 2-7 alpha helix are coiled together like the strands of a rope . Many coiled coil type proteins are involved in important biological functions such as the regulation of gene expression e.g....
. Cytoplasmic IF assemble into non-polar unit-length filaments (ULF) which then assemble into longer structures. Part of the assembly process includes a compaction step, in which ULF tighten and assume a smaller diameter. The reasons for this compaction are not well understood, and IF are routinely observed to have diameters ranging between 6 and 12nm.

The anti-parallel orientation of tetramers means that, unlike microtubules and microfilaments which have a plus end and a minus end, IFs lack polarity.

Also, as opposed to actin
Actin

Actin is a Globular_protein, roughly 42-kDa protein found in all Eukaryote where it may be present at concentrations of over 100 ?M. It is also one of the most highly-Conservation proteins, differing by no more than 20% in species as diverse as algae and humans....
 or tubulin
Tubulin

Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are a-tubulin and ?-tubulin, the proteins that make up microtubules....
, intermediate filaments do not contain a binding site
Binding site

In biochemistry, a binding site is a region on a protein, DNA, or RNA to which specific other molecules and ions — in this context collectively called Ligand , or more specifically, protein ligands — form a chemical bond....
 for a nucleoside triphosphate
Nucleoside triphosphate

Nucleoside triphosphate is a nucleoside with three phosphates. Natural nucleoside triphosphates include adenosine triphosphate , guanosine triphosphate , cytidine triphosphate , thymidine triphosphate and uridine triphosphate ....
.

Cytoplasmic IF do not undergo treadmilling
Treadmilling

Treadmilling is a phenomenon observed in many Cell cytoskeleton protein filament, especially in actin filaments and microtubules. It occurs when one end of a filament grows in length while the other end shrinks resulting in a section of filament seemingly "moving" across a stratum or the cytosol....
 like microtubules and actin fibers, but they are dynamic. For a review see: .

Types

There are about 70 different genes coding for various intermediate filament proteins. However, different kinds of IFs share basic characteristics: they are all polymers that generally measure between 9-11 nm in diameter when fully assembled.

IF are subcategorized into six types based on similarities in amino acid sequence and protein
Protein

Proteins are organic compounds made of amino acids arranged in a linear chain and joined together by peptide bonds between the carboxyl and amino groups of adjacent amino acid Residue ....
 structure.

Types I and II - Acidic and Basic Keratins

These proteins are the most diverse among IFs and constitute type I (acidic)
Type I cytokeratin

Type I keratins constitutes the Type I intermediate filaments of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells....
 and type II (basic)
Type II cytokeratin

Type II keratins constitutes the Type II intermediate filaments of the intracytoplasmatic cytoskeleton, which is present in all mammalian epithelial cells....
 IF proteins. The many isoforms are divided in two groups:
  • epithelial keratins (about 20) in epithelial cells (image to right)
  • trichocytic keratins (about 13) (hair keratin
    Hair keratin

    Hair keratin is a type of keratin found in hair and nail . There are two types of hair keratin:* the acidic type I hair keratin**type I hair keratin 1, ...
    s) which make up hair
    Hair

    Hair is a protein filament that epidermal growth from hair follicle deep within the dermis. The fine, soft hair found on many nonhuman mammals is typically called fur; wool is the characteristically curly hair found on sheep and goats....
    , nails
    Nail (anatomy)

    A nail is a horn -like structure at the end of an animal's finger or toe. See also claw....
    , horns
    Horn (anatomy)

    A horn is a pointed projection of the skin on the head of various mammals, consisting of a covering of horn surrounding a core of living bone....
     and reptilian
    Reptile

    Reptiles, or members of the class Reptilia, are air-breathing, cold-blooded vertebrates that have skin covered in scale as opposed to hair or feathers....
     scales
    Scale (zoology)

    In most biology nomenclature, a scale is a small rigid plate that grows out of an animal's skin to provide protection. In lepidopteran species, scales are plates on the surface of the insect wing, and provide coloration....
    .


Regardless of the group, keratins are either acidic or basic. Acidic and basic keratins bind each other to form acidic-basic heterodimers and these heterodimers then associate to make a keratin filament.

Type III

There are four proteins classed as type III IF proteins which may form homo- or heteropolymer
Heteropolymer

A heteropolymer or copolymer is a polymer derived from two monomeric species, as opposed to a homopolymer where only one monomer is used....
ic proteins.
  • Desmin
    Desmin

    Desmin is a type III intermediate filament found near the Z line in sarcomeres. It was first purified in 1977, the gene was characterized in 1989, and the first knock-out mouse was created in 1996....
     IFs are structural components of the sarcomere
    Sarcomere

    "A-band" redirects here. For other uses of the term see A band.A sarcomere is the basic unit of a muscle's cross-striated myofibril. Sarcomeres are multi-protein complexes composed of three different filament systems....
    s in muscle cells.
  • GFAP
    Glial fibrillary acidic protein

    Glial fibrillary acidic protein is an intermediate filament protein that is thought to be specific for astrocytes in CNS. Later it was shown that GFAP also is expressed by other cell types in CNS - ependymal cells....
     (glial fibrillary acidic protein) is found in astrocyte
    Astrocyte

    Astrocytes are characteristic star-shaped neuroglia cell in the brain and spinal cord. They perform many functions, including biochemical support of endothelial cells which form the blood-brain barrier, the provision of nutrients to the nervous tissue, and a principal role in the repair and scarring process of the brain and spinal cord fol...
    s and other glia.
  • Peripherin
    Peripherin

    Peripherin is a type of Intermediate filament.Found in subsets of neuronsExternal links...
     found in peripheral neurons.
  • Vimentin
    Vimentin

    Vimentin is a member of the intermediate filament family of proteins. Intermediate filaments are an important structural feature of eukaryotic cells....
    , the most widely distributed of all IF proteins, can be found in fibroblast
    Fibroblast

    A fibroblast is a type of cell that synthesizes the extracellular matrix and collagen , the structural framework for animal tissues, and play a critical role in wound healing....
    s, leukocytes, and blood vessel endothelial cells. They support the cellular membranes and keep some organelle
    Organelle

    In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid membrane....
    s in a fixed place within the cytoplasm
    Cytoplasm

    The cytoplasm is the part of a Cell that is enclosed within the plasma membrane. In eukaryote cells the cytoplasm contains organelles, such as mitochondrion, that are filled with liquid kept separate from the rest of the cytoplasm by biological membranes....
    .


Type IV


  • a-Internexin
    Internexin

    Internexin, alpha-internexin, is a Class IV intermediate filament approximately 66 Atomic mass unit. The protein was originally purified from rat optic nerve and spinal cord....
  • Neurofilament
    Neurofilament

    Neurofilaments are the 10 nanometer or intermediate filaments found specifically in neurons. The subunits of neurofilaments are related structurally to the 10nm or intermediate filaments of other tissues such as the keratin subunits, which make 10nm filaments expressed specifically in epithelia....
    s     - the type IV family of intermediate filaments that is found in high concentrations along the axon
    Axon

    An axon or nerve fiber is a long, slender projectionof a nerve cell, or neuron, that conducts action potentialaway from the neuron's cell body or soma....
    s of vertebrate neurons.
  • Nestin
    Nestin (protein)

    Nestin is a type VI intermediate filament protein. These intermediate filament proteins are expressed mostly in nerve cells where they are implicated in the radial growth of the axon....
  • Synemin
    Synemin

    Synemin, also called desmuslin, is an intermediate filament and, like other IFs, primarily functions to integrate mechanical stress and maintain structural integrity in eukaryotic cells....
  • Syncoilin
    Syncoilin

    Syncoilin is a muscle-specific intermediate filament, first isolated as a binding partner to DTNA, as determined by a yeast two-hybrid assay.Later, a yeast two-hybrid method was used to demonstrate that syncoilin is a binding partner of desmin....


Type V - Nuclear Lamins

  • Lamin
    Lamin

    Nuclear Lamins, also known as Class V intermediate filaments, are fibrous proteins providing structural function and transcriptional regulation in the cell nucleus....
    s
Lamins are fibrous proteins having structural function in the cell nucleus.

In metazoan cells there are A and B type lamins which differ in their length and pI. Human cells have three differentially regulated genes. B-type lamins are present in every cell. B type lamins, B1 and B2, are expressed from the LMNB1 and LMNB2 genes on 5q23 and 19q13, respectively. A-type lamins are only expressed following gastrulation
Gastrulation

Gastrulation is a phase early in the development of animal embryos, during which the morphology of the embryo is dramatically restructured by cell migration....
. Lamin A and C are the most common A-type lamins and are splice variants of the LMNA gene found at 1q21.

These proteins localize to two regions of the nuclear compartment, the nuclear lamina -- a proteinaceous structure layer subjacent to the inner surface of the nuclear envelope and throughout the nucleoplasm in the nucleoplasmic "veil".

Comparison of the lamins to vertebrate cytoskeletal IFs shows that lamins have an extra 42 residues (six heptads) within coil 1b. The c-terminal tail domain contains a nuclear localization signal (NLS), an Ig-fold like domain, and in most cases a carboxy-terminal CaaX box that is isoprenylated and carboxymethylated (lamin C does not have a CAAX box). Lamin A is further processed to remove the last 15 amino acids and its farnesylated cysteine.

During mitosis, lamins are phosphorylated by MPF which drives the disassembly of the lamina and the nuclear envelope.

Unclassified

phakinin philensin

Cell adhesion

At the plasma membrane, some keratins interact with desmosome
Desmosome

A desmosome, also known as macula adherens or macula adherentes , is a cell structure specialized for cell-to-cell cell adhesion....
s (cell-cell adhesion) and hemidesmosome
Hemidesmosome

Hemidesmosomes are very small stud- or rivet-like structures on the inner basal surface of keratinocytes in the epidermis of skin. They are similar in form to desmosomes when visualized by electron microscopy....
s (cell-matrix adhesion) via adapter proteins.

Associated proteins

Filaggrin
Filaggrin

Filaggrins are filament-associated proteins which bind to keratin fibers in Epitheliums.Individuals with truncation mutations in the gene coding for filaggrin are strongly predisposed to a severe form of dry skin, , and/or eczema ....
 binds to keratin fibers in epidermal cells. Plectin
Plectin

Plectin is a giant protein found in nearly all mammalian Cell which acts as a link between the three main components of the cytoskeleton: actin microfilaments, microtubules and intermediate filaments....
 links vimentin to other vimentin fibers, as well as to microfilaments, microtubules, and myosin
Myosin

Myosins are a large family of motor proteins found in eukaryotic Biological tissue. They are responsible for actin-based motility.Following the discovery, by Pollard and Korn, of enzymes with myosin-like function in Acanthamoeba, a large number of divergent myosin genes have been discovered throughout eukaryotes....
 II.

Keratin filaments in epithelial cells link to desmosome
Desmosome

A desmosome, also known as macula adherens or macula adherentes , is a cell structure specialized for cell-to-cell cell adhesion....
s(desmosomes connect the cytoskelton together) through plakoglobin
Plakoglobin

Plakoglobin was originally identified as a component of desmosome, where it can bind to the cadherin family member desmoglein.Plakoglobin also associates with classical cadherins such as E-cadherin; in that context, it was called gamma-catenin....
, desmoplakin
Desmoplakin

Desmoplakin is a protein associated with desmosomes.Desmoplakin, also known as DSP, is a human gene....
, desmoglein
Desmoglein

The desmogleins are a family of cadherins consisting of proteins DSG1, DSG2, DSG3, and DSG4. They play a role in the formation of desmosomes that join cells to one another....
s and desmocollin
Desmocollin

Desmocollin is a type of cadherin.Specifically, it can refer to one of the following human genes :* DSC1* DSC2* DSC3References...
s; desmin
Desmin

Desmin is a type III intermediate filament found near the Z line in sarcomeres. It was first purified in 1977, the gene was characterized in 1989, and the first knock-out mouse was created in 1996....
 filaments are connected in a similar way in heart muscle cells.

Diseases arising from mutations in IF genes


  • Epidermolysis bullosa simplex
    Epidermolysis bullosa simplex

    Epidermolysis bullosa simplex is a disorder resulting from mutations in the genes encoding keratin 5 or keratin 14.Blister formation of EBS is within the basal keratinocyte of the epidermis....
    ; K5 or K14 mutation
  • Laminopathies are a family of diseases caused by mutations in nuclear lamins and include Hutchinson Gilford Progeria Syndrome and various lipodystrophies and cardiomyopathies among others.
  • , a comprehensive database of human intermediate filament proteins, their associated variations and diseases.


External links