Intermediate filaments

Description of Cytoskeletal elements, Intermediate filaments, characteristics, EBS,ALS, cell Junctions

1. Intermediate Filaments Dr. Sarita Nanda Biochemistry Department Daulat Ram College

2. Introduction They have diameter between 8-11nm They provide mechanical strength to cells and tissues They provide scaffold for localization of cellular processes

3. Intermediate Filament Proteins They are composed of variety of proteins There are 65 different intermediate filament Type I, II, III,IV, V and VI proteins Type I is acidic keratin which is of size 40-69 KD found in epithelial cells Type II is neutral/basic keratin of 50-70KD found in epithelial cells Type III is vimentin which is of 54 KD found in fibroblasts

4. Intermediate Filament Proteins Type IV is neurofilament of 67-200 KD present in neuron Type V is nuclear lamin which is of 60-79 KD which is present in nuclear lamina Type VI is Nestin which is of 200KD which is present in stem cells especially of CNS

5. Assembly of Intermediate Filament The first stage is it forms dimers. The dimers form tetramers The tetramers assemble end to end to form protofilament The tetramers organize to form octamer They are arranged in antiparallel manner. Thus they are apolar. They do not have distinct ends i.e. barbed or pointed end of intermediate filament.

6. Assembly of Intermediate Filaments

7. Intermediate Filaments

8. Characteristics Intermediate filaments are generally more stable than actin filaments or microtubules They do not exhibit dynamic behavior associated with other cytoskeleton Intermediate filament protein can be modified by phosphorylation which can regulate their assembly and disassembly. This is observed in nuclear lamin Cytoplasmic intermediate filaments such as vimentin are also phosphorylated which lead to their disassembly and reorganization in dividing or migrating cells

9. Intracellular Organization of Intermediate Filament Both keratin and vimentin attach to nuclear envelop serving to position and anchor nucleus within the cell Intermediate filament associate with associate with other cytoskeleton elements Intermediate filaments form junctions Desmosomes: cell-cell Hemidesmosome-cell-matrix

10. Junction Proteins On the cytoplasmic the junctions are associated with plakins Plakins bind intermediate filaments Hemidesmosomes bind to different member od plakins i.e. Plectins bind to other cytoskeleton elements Desmin connects individual actin myosin assemblies of muscle cell both one to another and to the plasma membrane Neurofilaments are major intermediate filaments of motor neurons , NF- L, NF-M, NF-H

11. Junction Proteins They help to support and stabilize other cytoskeleton in thin extension of nerve cells

12. Junction Proteins Hemidesmosomes

13. Diseases of Intermediate filament Epidermis bullous simplex(EBS) Mutant keratin gene form skin blister resulting from cell lysis after minor trauma Lou Gehrig's disease (Amyotrophic lateral sclerosis, ALS): leads to progressive loss of motor neurons which lead to muscle atrophy, paralysis and eventual death

14. Diseases of Intermediate Filaments

15. Diseases of Intermediate Filaments Epidermolysis Bullosa Simplex (EBS)