Cytoskeleton remodeling - Keratin filaments

Keratin filaments

Cytoskeleton in most eukaryotic cells consists of three distinct, yet interconnected, filament systems: Actin filaments, Microtubules and intermediate filaments. Cell assembly is integrated by the network of intermediate filaments (IFs) and by their interactions with other cytoskeleton structural elements defining cytoarchitecture and cytodynamics.

IF network is critically involved in cell shape control and imparts intracellular mechanical strength. The family of IF proteins has five sub-families. Four of the sub-families are localized in the cytoplasm, whereas the fifth sub-family is found in the nucleus. Expression patterns of cytoplasmic IFs are cell- and tissue-type specific.

The main IF protein is found in epithelial cells is Keratin and in fibroblasts it is Vimentin. Keratin IFs are obligate co-polymers of acidic and basic cytokeratins [1], [2].

IF networks are cross-linked by special binding proteins, e.g., Plectin, BPAG1, Desmoplakin, Envoplakin, Periplakin, Epiplakin, Trichoplein and Plakophilins [3], [4], [5], [6]. These proteins maintain cell and tissue integrity by coordinated interconnection of three distinct cytoskeletal filament systems, and anchoring them to membrane complexes.

Assembly, disassembly and subcellular organization of IFs is regulated by kinases, e.g., by Mitogen-activated protein kinases 8-10 (JNK(MAPK8-10)) and Cell division cycle 2 (CDK1) [7], [8].

References:

1. Strelkov SV, Herrmann H, Aebi U
   Molecular architecture of intermediate filaments. BioEssays : news and reviews in molecular, cellular and developmental biology 2003 Mar;25(3):243-51
2. Helfand BT, Chang L, Goldman RD
   Intermediate filaments are dynamic and motile elements of cellular architecture. Journal of cell science 2004 Jan 15;117(Pt 2):133-41
3. Leung CL, Green KJ, Liem RK
   Plakins: a family of versatile cytolinker proteins. Trends in cell biology 2002 Jan;12(1):37-45
4. Fontao L, Favre B, Riou S, Geerts D, Jaunin F, Saurat JH, Green KJ, Sonnenberg A, Borradori L
   Interaction of the bullous pemphigoid antigen 1 (BP230) and desmoplakin with intermediate filaments is mediated by distinct sequences within their COOH terminus. Molecular biology of the cell 2003 May;14(5):1978-92
5. Jang SI, Kalinin A, Takahashi K, Marekov LN, Steinert PM
   Characterization of human epiplakin: RNAi-mediated epiplakin depletion leads to the disruption of keratin and vimentin IF networks. Journal of cell science 2005 Feb 15;118(Pt 4):781-93
6. Nishizawa M, Izawa I, Inoko A, Hayashi Y, Nagata K, Yokoyama T, Usukura J, Inagaki M
   Identification of trichoplein, a novel keratin filament-binding protein. Journal of cell science 2005 Mar 1;118(Pt 5):1081-90
7. Ku NO, Omary MB
   Phosphorylation of human keratin 8 in vivo at conserved head domain serine 23 and at epidermal growth factor-stimulated tail domain serine 431. The Journal of biological chemistry 1997 Mar 14;272(11):7556-64
8. He T, Stepulak A, Holmstrom TH, Omary MB, Eriksson JE
   The intermediate filament protein keratin 8 is a novel cytoplasmic substrate for c-Jun N-terminal kinase. The Journal of biological chemistry 2002 Mar 29;277(13):10767-74