What are intermediate filaments?

Intermediate filaments:

                                    Intermediate filaments are those proteins which form the basic mechanical support for the cells of the vertebrates and invertebrates. These are named so because the average diameter of these filaments(10 - 12 nm) lies between the diameter of the actin microfilaments( 7 - 10 nm) and the microtubules(25 nm).

                                    There are around 6 subtypes of the intermediate filament superfamily.

Intermediate filaments Functions:

These intermediate filaments are involved in the stabilization of the organelles like the nucleus or they may sometimes involved in the specialized junctions.

                                     Another important use of the intermediate filaments is that a large number of tumors are look-alike when examined under the microscope using basic stains. But, they must be identified precisely to deliver the needed therapy and to improve the prognosis of the patient. In such cases, antibodies specific to the specific type of intermediate filaments come into play.

 The important intermediate filaments are as follows:

1.Cytokeratin:

                                    These filaments are named from CK 1 to CK 20. These types of intermediate filaments are mostly found in the epithelial cells. These filaments are useful as an Immunological marker for epithelial differentiation.

                                    These types of intermediate filaments are useful in finding the steatohepatitis. They are called by a special name known as "Mallory-Denke bodies".

                          

·   These types of filaments are important in corticotrope adenomas which produce ACTH. In light microscopy, these fibers are seen as "Crooke hyalinization".

·  Somatotrope adenomas have special cytoplasmic inclusion called "fibrous bodies", which contain keratin intermediate filaments of type 8.

·  Keratohyaline granules present in the granular layer of the skin contains profilaggrin, which is a type of intermediate filament under this subtype of IF.

                

                                   It has been found that the defect in the gene coding for the cytokeratin intermediate filaments is associated with the pathogenesis of Epidermolytic type of epidermolysis bullosa.

2.Vimentin:

                    These filaments are found in the mesenchymal cells. These type of filaments forms the markers for the mesenchymal differentiation. The immunohistochemical staining of vimentin shows a red-brown reaction.

                    Vimentin filaments are involved in the wound contraction in case of larger size surface wounds.

                    These IF are found in the cytoplasm of the rhabdoid tumor(occasionally it shows immunopositive for smooth muscle actin and keratin also).

                    Vimentin filaments are found to be associated with the pathogenesis of Rheumatoid arthritis in the formation of the immune complexes that deposit in the joints.

                     Vimentin is found to be positive in cases of cardiac angiosarcomas, osteosarcomas and especially in the case of Mesotheliomas.

                           Additionally, vimentin is found to be associated with HER2 negative breast cancers like Basal-like cancers and "Claudin low tumors".

 "A general saying that, Vimentin is mostly found positive in cases of sarcomas whereas Cytokeratins are found to be positive in cases of carcinomas".

3.Desmin:

                 It is a muscle-specific intermediate filament. It is coded by the gene DES. Desmin provides structural integrity in the sarcomere (which is the basic unit of the muscle). This protein acts as an immunological marker for the myoid (muscle-like) differentiation.

                  They form important components in the pathogenesis of the "Dilated cardiomyopathy"(Arrhythmogenic Cardiomyopathy ), "Rhabdomyosarcoma"(along with other markers like MYOD1 and myogenin)," leiomyosarcomas".

             Desmin also is involved in wound contraction just like vimentin.

4. Neurofilaments:

            These are the intermediate filaments similar to neurons with the diameter measuring 10nm. They maintain the structural integrity in the axons. They form the immunological marker for neuronal differentiation. They are mainly associated with conditions like corticobasal degeneration, tauopathies(including Alzheimer's disease), Amyotrophic lateral sclerosis.

           Lewy bodies present in these conditions on ultrastructural examination reveals neurofilaments along together with ubiquitin and α-synuclein.

              

5.Glial Fibrillary Acidic Protein(GFAP):

                 These are the supportive filaments of the supportive cells in the central nervous systems.

These filaments are coded by the gene GFAP. They are the marker s of the glial differentiation. Glial cells are those types of supporting cells that surround the neurons in the human body and even insulates them.

               They are found to be immunohistochemically positive in cases of Juvenile pilocytic astrocytoma.

 

               Mutations in the GFAP is associated with leukodystrophies like Alexander disease( which is an autosomal recessive condition).

                

               There are many different kinds of glial cells which include, oligodendrocytes, astrocytes, ependymal cells, Schwann cells, microglia, and satellite cells.

                Astrocytes, when subjected to an acute injury will upregulate the synthesis of the GFAP. These proteins are then organized to form various structural proteins and filaments of the astrocytes.

              On the other hand, if the astrocytes are subjected to chronic injury then, there can be an inclusion body formed which is composed of densely packed glial intermediate filaments, named as Rosenthal fibers ( seen in Alexander disease, pilocytic astrocytoma).

               

                A low-grade astrocytoma called Gemistocytic astrocytoma, which has cells filled with glial intermediate filaments.

6.Lamins:

             These are the structural proteins present inside of the nuclear envelope that provides structural integrity to the nucleus( by maintaining the chromatin organization).

                Defect in the LMNA (gene coding lamin A) will lead to a premature aging condition called Hutchinson Gilford progeria syndrome.