1: Eur J Cell Biol. 2004 Dec;83(11-12):735-46.


Great promises yet to be fulfilled: defining keratin intermediate filament function in vivo.

Coulombe PA, Tong X, Mazzalupo S, Wang Z, Wong P.

Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. coulombe@jhmi.edu

Keratins are abundant proteins in epithelial cells, in which they occur as a cytoplasmic network of 10 - 12 nm wide intermediate filaments (IFs). They are encoded by a large family of conserved genes in mammals, with more than 50 individual members partitioned into two sequence types. A strict requirement for the heteropolymerization of type I and type II keratin proteins during filament formation underlies the pairwise transcriptional regulation of keratin genes. In addition, individual pairs are regulated in a tissue-type and differentiation-specific manner. Elucidating the rationale behind the diversity and differential distribution of keratin proteins offers the promise of novel insight into epithelial biology. At present, we know that keratin IFs act as resilient yet pliable scaffolds that endow epithelial cells with the ability to sustain mechanical and non-mechanical stresses. Accordingly, inherited mutations altering the coding sequence of keratins underlie several epithelial fragility disorders. In addition, keratin IFs influence the cellular response to pro-apoptotic signals in specific settings, and the routing of membrane proteins in polarized epithelia. Here we review studies focused on a subset of keratin genes, K6, K16 and K17, showing a complex regulation in vivo, including a widely known upregulation during wound repair and in diseased skin. Progress in defining the function of these and other keratins through gene manipulation in mice has been hampered by functional redundancy within the family. Still, detailed studies of the phenotype exhibited by K6 and K17 null mice yielded novel insight into the properties and function of keratin IFs in vivo.

Publication Types:
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 15679118 [PubMed - indexed for MEDLINE]

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2: Exp Cell Res. 2004 Nov 15;301(1):1-7.


Desmin: a major intermediate filament protein essential for the structural integrity and function of muscle.

Paulin D, Li Z.

Biologie moléculaire de la différenciation, Université Paris, 75251 Paris, France. paulin@ccr.jussieu.fr

Desmin is a muscle-specific protein and a key subunit of the intermediate filament in cardiac, skeletal and smooth muscles. Desmin filaments are mainly located at the periphery of Z-disk of striated muscles and at the dense bodies of smooth muscle cells, and they have been postulated to play a critical role in the maintenance of structural and mechanical integrity of the contractile apparatus in muscle tissues. This review summarizes the findings in the regulation of the desmin gene and function of the desmin protein. The expression of desmin gene is regulated by a combination of different transcription control regions in muscle cells. The results from mice deficient in desmin reveal the fundamental role of desmin filaments in cell architecture, force transmission and mitochondrial function. Mice lacking desmin postnatally develop a dilated cardiomyopathy, a skeletal myopathy and smooth muscle defects. Some of desmin-related myopathies are attributable to a missense mutations and deletions in the desmin gene. Other desmin-related myopathies, in which the desmin gene is not mutated, could be related to mutations of the genes encoding the proteins that interact with desmin.

Publication Types:
Review

PMID: 15501438 [PubMed - indexed for MEDLINE]

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3: Subcell Biochem. 1998;31:1-33.


Fish intermediate filament proteins in structure, evolution, and function.

Markl J, Schechter N.

Institute of Zoology, Johannes Gutenberg University of Mainz, Germany.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 9932488 [PubMed - indexed for MEDLINE]

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4: J Struct Biol. 1998;122(1-2):67-75.


Hard alpha-keratin intermediate filament chains: substructure of the N- and C-terminal domains and the predicted structure and function of the C-terminal domains of type I and type II chains.

Parry DA, North AC.

Institute of Fundamental Sciences, Massey University, Palmerston North, New Zealand.

The quantity of sequence data now available for both Type I and Type II hard alpha-keratin IF proteins makes it possible to analyze their N- and C-terminal domains and ascertain features of likely structural and/or functional importance. The N-terminal domains of both chain types can be divided into acidic (NA) and basic (NB) subdomains, where NA is 29 and 34 residues long, respectively, for Type I and II chains and is located immediately adjacent to the end of the rod domain. NB constitutes the remainder of the N-terminal domain and is about 27 and 70 residues long for the two chain types, respectively. The glycine residue contents, however, are high in NA(I) and NB(II), but low in NA(II) and NB(I). Subdomain NB(II) contains four consecutive nonapeptide quasirepeats of the form GGGFGYRSX. The C-terminal domain of Type I chains, termed C(I), is characterized by a PCX motif repeated 10 times, 7 of them contiguously. From an analysis of the conformation of like peptides from crystal structures it has been shown that this region will probably adopt a polyproline II left-handed helical structure with three residues per turn. In contrast, the C-terminal domain of Type II hard alpha-keratin chains (known as C(II)) contains a periodic distribution of hydrophobicities that, together with other predictive techniques, allow its conformation (a twisted four-stranded antiparallel beta-sheet) to be predicted with some degree of confidence. In addition, it is possible to suggest two partners with which this domain will interact. The first is with segment L12 in the rod domain and the second is with another C(II) domain in an antiparallel neighboring molecule. The latter possibility appears most likely. In either case the aggregation would likely serve to stabilize the molecular assembly through the interaction of two beta-sheets via their apolar faces and, in so doing, would position a number of cysteine residues in external positions that would allow them to form a number of covalent disulfide bonds with other molecules. Copyright 1998 Academic Press.

Publication Types:
Review

PMID: 9724606 [PubMed - indexed for MEDLINE]

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5: Curr Top Dev Biol. 1995;31:455-86.


Intermediate filament organization, reorganization, and function in the clawed frog Xenopus.

Klymkowsky MW.

Department of Molecular, Cellular, and Developmental Biology, University of Colorado, Boulder 80309, USA.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.
Review

PMID: 8746673 [PubMed - indexed for MEDLINE]

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6: Int Rev Cytol. 1994;154:1-103.


Intermediate filament proteins: cytoskeletal elements with gene-regulatory function?

Traub P, Shoeman RL.

Max-Planck-Institut für Zellbiologie, Ladenburg/Heidelberg, Germany.

Publication Types:
Comparative Study
Review

PMID: 8083030 [PubMed - indexed for MEDLINE]

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7: Cell Motil Cytoskeleton. 1991;19(2):67-79.


Recent insights into the assembly, dynamics, and function of intermediate filament networks.

Skalli O, Goldman RD.

Department of Cell, Molecular, and Structural Biology, Northwestern University Medical School, Chicago, IL 60611.

Publication Types:
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

PMID: 1878980 [PubMed - indexed for MEDLINE]

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8: Verh Dtsch Ges Pathol. 1990;74:335-49.


[Cytoskeleton--function and pathology: studies on the pathology of the intermediate filament cytoskeleton of liver cells]

[Article in German]

Denk H, Zatloukal K, Preisegger KH.

Pathologisches Institut, Universität Graz.

Microfilaments, microtubules and intermediate filaments (IF) are major filamentous components of the cytoskeleton and play a role in the modulation of cell shape, in cellular movements, cellular stability, intracellular organisation as well as cell-to-cell and cell-to-stroma interactions. Particular interest was concentrated in the last few years on IF because of their cell type-specificity and, consequently, their suitability as cell markers in diagnostic pathology. Despite their apparent stability, IF are dynamic structures which may be modified under pathologic conditions. In recent years, pathologic alterations related to the IF cytoskeleton have been described in a diversity of chronic and degenerative disorders, including alcoholic hepatitis and neurologic diseases (e.g. M. Alzheimer, M. Parkinson). Our studies were particularly devoted to the elucidation of the pathogenesis of severe alcoholic liver injury (alcoholic hepatitis), which is associated with inflammation, liver cell degeneration and necrosis and morphologically characterized by the appearance of cytoplasmic hyaline inclusions (i.e., Mallory bodies). In the present review morphologic, immunologic and biochemical studies on nature and pathogenesis of Mallory bodies are summarized. Moreover, similarities between Mallory bodies and other cytoskeleton-related inclusion bodies suggest common routes of pathogenesis. Consequently, studies along these lines may not only lead to the understanding of mechanisms involved in alcoholic injury but may also provide information on general principles of cell damage as well as on regulation and function of the IF cytoskeleton.

Publication Types:
English Abstract
Research Support, Non-U.S. Gov't
Review

PMID: 1708610 [PubMed - indexed for MEDLINE]