Intermediate Filaments

Intermediate Filaments

Normand Marceau, Anne Loranger, Stephane Gilbert
ISBN: 9781615045402 | PDF ISBN: 9781615045419
Copyright © 2013 | 112 Pages | Publication Date: 06/01/2014

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Intermediate filaments (IFs), in concert with microfilaments (MFs) and microtubules (MTs), form the cytoskeleton, and each of these fibrillar networks exhibits rather unique structural and functional characteristics. Intermediate filaments were discovered in eukaryotic cells in the late 1960s, and their name comes from the fact that their diameter is intermediate between MFs and MTs. In contrast to the latter, IFs constitute a network that extends from the nuclear envelope throughout the cytoplasm, and in many cases, interact with cell surface domains involved in cell-cell and cell- matrix interactions. Several key features of their expression, assembly, structure and dynamics are highlighted in this eBook. For instance, IF proteins are encoded by several genes, which are classified into six types reflecting the tissues (cells) of origin. Moreover, IF proteins contain a conserved central ?-helical (rod) domain flanked by N-terminal (head) and C-terminal (tail) globular domains that enables assembly of fibrous IFs exhibiting a tripartite structure. Although the rod domain is responsible for the formation of the coiled-coil framework and yields the main driving force during the IF protein assembly, the head and tail domains contribute to most of the structural heterogeneity of IF organization and undergo several types of post-translational modifications. Furthermore, the development of gene targeting methods to genetically knockout the expression of the IF genes in mice has uncovered the mechanical versus non-mechanical features of the IF networks, namely, their involvement in cell response to diverse forms of stress, growth stimulation, migration, or death insults. Finally, there is accumulating evidence revealing that the tissue and cell-type expression of IF genes reflects itself in the presence of causal or predisposition mutations responsible for numerous human tissue-specific diseases, known as IF-pathies.

Table of Contents

List of Abbreviations
Introduction
IFs as a Multigene Family of Filamentous Proteins
Nuclear Lamina
IF Functional Interplay with Cell Surface Domains and Organelles
IFs and Cell Specialization
IF Relevance to Human Diseases
Conclusion
References
Author Biographies

About the Author(s)

Normand Marceau, Laval University, Quebec City, Canada
Normand Marceau, Ph.D., is professor in the Department of Molecular Biology, Medical Biochemistry and Pathology at Laval University in Quebec City, Canada. He received his Bachelor Engineering Physics degree from the same university in 1966, and then his M.Sc. (1968) and Ph.D. (1971) in Medical Biophysics from the University of Toronto. He has been successful in training quite a few performing graduate students who have found and maintained a science-related position in basic transdisciplinary academic research. His interest in Intermediate Filaments originated from a previous research program on the identification and fate of liver cell progenitors in normal versus cancerous development, where distinct pairs of keratins (the largest IF protein family) were found in the early 1980s to provide reliable markers of differentiating liver progenitors. A major innovative event took place in 1992, when H. Baribault (a former graduate student) and R. G. Oshima succeeded in generating the first IF gene-null mice, that is, the keratin 8-null mice. Notably, hepatocytes and hepatoma cells expressed solely the keratin 8/18 pair, which means that the loss of one keratin leads to the degradation of its partner, thus providing animal models of choice to address the IF-dependent modulation of hepatic cell activities. Dr. Marceau's enviable contribution to the IF field is particularly associated with the keratin 8/18 IF regulation of cell death, metabolism, migration, and contraction, in relation to liver diseases, including cancer.

Anne Loranger, Laval University, Quebec City, Canada
Anne Loranger received her B.Sc. in medical biology from the Universite du Quebec a Trois-Rivieres (UQTR) and her Ph.D. in pharmacology from the University of Montreal, Canada, in 1992. She has been a research associate and a lab manager in Dr. Normand Marceau Laboratory and the Cell Imaging Unit since 1994. She initiated much of the early IF-related research in the lab and was one of the first to uncover the involvement of simple epithelium keratins in the maintenance of hepatocyte integrity.

Stephane Gilbert, Laval University, Quebec City, Canada
Stephane Gilbert received his B.Sc. in biochemistry in 1994 and his Ph.D. in molecular and cellular biology in 2000 from Laval University, Quebec, Canada. He is a research associate in Dr. Normand Marceau Laboratory. He published and collaborated on many articles in the intermediate filament field, and was one of the first to demonstrate the role of intermediate filaments in apoptosis regulation.

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