Cytoskeleton in Specialized Tissues and in Pathological States PDF
Preview Cytoskeleton in Specialized Tissues and in Pathological States
LIST OF CONTRIBUTORS Shunnosuke Abe Laboratory of Molecular Cell Biology Enime University Matsuyama, Japan Bjorn A. Afzelius Department of Ultrastructure Research The Wenner-Gren Institute University of Stockholm Tommy Andersson Department of Cell Biology Faculty of Health Sciences University Hospital of Linkoping Sweden Loranne Agius Department of Medicine The University of Newcastle upon Tyne England Jane E. Barker The Jackson Laboratory Bar Harbor, Maine William M. Bement Department of Zoology University of Washington, Madison El. Benedetti Institut Jacques Monad CNRS Universite Paris H. Bloemendal Department of Biochemistry University of Nijmegen Max 5. Bush Developmental Biology Research Centre The Randall Institute Eric Da vies Botany Department North Carolina State University VII LIST OF CONTRIBUTORS jl. Dufier Service d'Ophtalmologie Hopital Necker-Enfants Maiades Paris, France I. Dunia Instltut Jacques Monad CNRS Universite Paris Peter A.M. Eagles Biomedical Sciences Division The Randall Institute Maria Fallman Department of Medical Microbiology Faculty of Health Sciences University Hospital of Linkoping Sweden Becky D. Fillingham School of Biological Sciences University of Nebraska Phillip R. Gordon-Weeks Biomedical Sciences Division and Developmental Biology Research Centre The Randall Institute Carina Hell berg Department of Cell Biology Faculty of Health Sciences University Hospital of Linkoping Sweden John E. Hesketh Rowett Research Institute Aberdeen, Scotland Pirjo Inki Turku Centre for Biotechnology University of Turku Finland Markka Jalkanen Turku Centre for Biotechnology University of Turku Finland Stuart Kellie Yamanouchi Research Institute Littlemore Hospital Oxford Wim Kuijpers Department of Otorhinolaryngology University of Nijmegen The Netherlands List of Contributors Pel<ka Kur\<i Department of Bacteriology and Immunology University of Helsinki Department of Cell Biology Faculty of Health Sciences Ragnhild Lofgren University Hospital of Linkoping Sweden Cell and Molecular Biology of Bone and Cartilage Abderrahim Lomri Hopital Lariboislere Paris Ronald B. Luftig Department of Microbiology, Immunology, and Parasitology Louisiana State University Medical Center Dennis C. Macejak Cell Biology Ribozyme Pharmaceuticals Inc. Boulder, Colorado Pierre J. Marie Cell and Molecular Biology of Bone and Cartilage Hopital Larlbolsiere Paris Mark S. Mooseker Departments of Biology, Cell Biology, and Pathology Yale University Janet Ng-Sikorski Department of Cell Biology Faculty of Health Services University Hospital of Linkoping Sweden Eijiro Ozawa National Institute of Neurosclence National Center of Neurology and Psychiatry Tokyo Ian F. Pryme Department of Biochemistry and Molecular Biology University of Bergen Bergen, Norway LIST OF CONTRIBUTORS Frans C.S. Ramaekers Department of Molecular Cell Biology and Genetics University of Limburg The Netherlands Eva Sarndahl Departments of Cell Biology and Medical Microbiology Faculty of Health Services University Hospital of Linkoping Sweden David L Scott Department of Rheumatology King's College Hospital London Yit Kim Seng Ministry of Health Phnom Penh, Cambodia Anita Sjolander Department of Cell Biology Faculty of Health Services University Hospital of Linkoping Sweden Atsushi Suzuki National Institute of Neuroscience National Center of Neurology and Psychiatry Tokyo INTRODUCTION The cytoskeleton has many features, for example, the basic building blocks and transport functions of microtubules, myosin motor molecules, and actin microfila ments, which are conserved between cell types and even between organisms. However, in addition there are certain features of organization, regulation, or function which are specific to different cell or tissue types. Increasing knowledge of the properties of the cytoskeleton during normal cell function has been paralleled by an awareness that the cytoskeleton plays important roles in disease processes and cell pathology. It is now clear that abnormalities in the cytoskeleton can have sufficient impact on cell physiology that altered cell function and disease follow. In this last volume of the The Cytoskeleton, A Multi- Volume Treatise the chapters deal with aspects of the cytoskeleton which reflect the specialized functions of the different cell types and also describe examples of changes in the cytoskeleton which occur during various pathological states. These studies bring the exciting area of cytoskeleton research into the domain of medical science. Although the hepatocyte cytoskeleton shares many features with the cytoskeleton of cultured fibroblast cell lines, in addition, as described by Agius, it shows some unique features such as associations with Mallory bodies and the bile caniculus. One of the best known examples of a specialized cytoskeleton is that of the intestinal epithelium where the actin is bundled to form the structural core of the microvilli which line the absorptive surface. The details of the organization of the enterocyte cytoskeleton are described by Bement and Mooseker; this area is one of growing xi xli INTRODUCTION medical interest because the subversion of cytoskeletal organization by a number of pathogenic bacteria appears involved in the invasion process. Expression of cytoskeletal proteins also changes during cell differentiation and development and, as described by Kuijpers and Ramaekers, this is well-illustrated in another epithe lium, in this case the epithelial cells of the inner ear. Other aspects of infection are also related to functions of the cytoskeleton. The chapter by Andersson et al. describes the role of the cytoskeleton in the movements of the highly motile neutrophils and how interactions between cell signaling systems and the cytoskeleton may be involved in regulation of motility and phagocytosis in these cells; interestingly, cytoskeleton dysfunction is associated with increased susceptibility to infection. In addition, Macejak and Luftig describe the changes which occur during viral infection. The cytoskeleton also has well-defined functions in intracellular transport and the formation of links between cells and the extracellular matrix. These functions are of particular importance in tissues such as brain and bone. The neuronal cytoskeleton and its specializations in terms of axonal transport, dendrite structure, and nerve growth are described by Gordon-Weeks et al., while the role of the cytoskeleton in bone cell biology (for example, bone resorption), particularly the ability of osteoblasts and osteoclasts to respond to the extracellular matrix, is the subject of the chapter by Lomri and Marie. Modem molecular and genetic techniques have proved very powerful in the detection of lesions which underlie many pathological abnormalities, and this has also been the case with regard to the cytoskeleton. Such research has led to the identification of defects in the cytoskeleton in a number of clinical conditions, for example, defects in keratins in human skin diseases and, as described by Barker in the first chapter, defects in the membrane cytoskeleton in diseases of the erythro cyte. A further example is represented by defects in the muscle membrane cy toskeleton in muscular dystrophies, as described by Ozawa and Suzuki in a later chapter. As described in chapters in Volume 2 of this treatise, the cytoskeleton is apparently associated with both membrane signaling systems and with the protein synthetic apparatus. Since signaling systems, cell shape and growth, and cell adhesion are all altered during cell transformation and cell malignancy, it would therefore seem likely that there may be altered cytoskeleton function in malignant cells. Much attention has been given to this area of research and it is described in detail in the chapters by Kellie and by Inki and Jalkanen. The chapter by Benedetti et al. describes how alterations in both membrane cytoskeleton and the intermediate filaments are associated with a variety of patho logical conditions of the lens, such as opacity and cataract formation. As discussed by Scott and Kurki intermediate filaments also appear to be involved in the pathology of rheumatoid arthritis. Microtubules form the structural basis of cilia. Introduction xiii flagella, and sperm tails and defects in these can give rise to impaired motile function; this is described in the case of sperm tails by Afzelius. Another chapter deals not with a specialized tissue but with the huge area of plant cell cytoskeleton. Less is known about the cytoskeleton in plants because of inherent methodological difficulties but the chapter by Davies et al. gives an up-to-date account of the way the cytoskeleton may be involved in the specialized features and functions of plant cells. John E. Hesketh and Ian R Pryme Editors RED CELL CYTOSKELETAL ABNORMALITIES Jane E. Barker I. Red Cell Membrane Proteins 1 II. Diseases Involving RBC Structural Proteins 4 A. Disease Nomenclature 4 B. Chromosomal Assignment of Genes Encoding Cytoskeletal Proteins . ... 5 C. BiochemicalandMolecular Studies of Hemolytic Anemias 7 III. Future Perspectives 28 Acknowledgments 29 References 29 I. RED CELL MEMBRANE PROTEINS The human red blood cell (rbc), despite its inability to replace nuclear encoded proteins, is a dynamic entity that must deform multiple times during its 120-day life span and predicted 500,000 circuits of the body. Structural support is provided by cytoskeletal proteins aligned in a two dimensional lattice that parallels and is closely apposed to the membrane lipid bilayer. The deformable lattice binds unique cross-linking proteins that interact with proteins embedded in and protruding bidirectionally through the cell membrane. Proteins important to this review are: The Cytoskeleton, Volume 3, pages 1-42. Copyright © 1996 by JAI Press Inc. All rights of reproduction in any form reserved. ISBN: 1-55938-689-4 1 2 JANE E. BARKER the structural proteins—a and p spectrin, which comprise 25% of the rbc protein, and actin; the two integral membrane proteins—band 3 (the anion exchanger) and glycophorin C; and the membrane-structural protein linkers—^band 4.1, band 4.2 (pallidin), and ankyrin. Except for actin and glycophorin C, mutations in the genes encoding each of these proteins cause membrane disorders that can be sufficiently severe to be life threatening. The cytoskeleton is constructed during the differentiation of rbcs from immature precursors. In early erythroblasts, the a and P spectrin monomers, are synthesized in a 3:1 ratio concurrently with ankyrin but membrane incorporation is minimal and the proteins are unstable (Hanspal et al., 1992; Woods and Lazarides, 1988). In late erythroblasts, spectrin and ankyrin synthesis is dramatically reduced, but stable membrane recruitment occurs concomitant with increased synthesis of bands 3 and 4.1. It is believed that band 3 is the primary membrane spectrin nucleation site since rbcs that are fragile due to deficiency of band 4.1 show no dramatic spectrin decrease (Smith et al., 1983). Interactions between the various proteins are well-characterized but the actual mechanics of membrane assembly is not clear because studies have, of necessity, been performed in vitro rather than in vivo. In vitro, nucleation sites at the carboxy terminus of a spectrin and the amino terminus of p spectrin align and the monomers wrap around one another to form antiparallel heterodimers (Speicher et al., 1992). At the head end (amino terminus of a and carboxy terminus of P), two or more (Morrow and Marchesi, 1981; Ursiti et al., 1991) heterodimers fuse to form tetramers and higher oligomers. The tail end (carboxy terminus of a and amino terminus of P) contains specific actin-binding sites also found in a actinin, dystro phin, and so forth (Dubreuil, 1991) where F-actin polymers attach (Cohen et al., 1980). The junctional complex at the tail must attract other a/p tetramers since electron micrographs show spectrin aborization at the actin junctions (Liu et al., 1987). In the presence of the membrane linker band 4.1, spectrin binding to actin is enhanced. Saturation studies show that each actin monomer can bind a spectrin dimer in vitro (Cohen and Foley, 1984), although interactions in vivo are probably less extensive and modulated by band 4.9 and adducin. The spectrin network is attached to the membrane linkers, band 4.1 and ankyrin, at two different sites on the spectrin dimer (Tyler et al., 1979, 1980). A specific 8 kD band 4.1 peptide promotes spectrin/actin binding (Correas et al., 1986a, 1986b). Band 4.1 stabilizes the weak associations between spectrin and actin but will only interact with actin in the presence of a and p spectrin heterodimers (Cohen and Langley, 1984). The 4.1 binding affinity is determined not by the a spectrin monomer but by the p spectrin in the heterodimer (Coleman et al., 1987). The specific binding site on p spectrin for band 4.1 is in the actin binding region (Becker et al., 1990) while the 4.1 binding sites on actin, if they exist, are, as yet, unknown. It is unclear whether a spectrin plays a direct role in the interaction with band 4.1 or induces conformational changes in the heterodimer that permit band 4.1/p spectrin interactions. As noted previously (Smith et al., 1983), 4.1/membrane Red Cell Cytoskeletal Abnormalities 3 binding sites may not be as important for stabilizing the cytoskeleton as predicted earlier. Ankyrin, on the other hand, binds with high affinity (Bennett and Stenbuck, 1979) to a specific site near the carboxy terminus on P spectrin (Kennedy et al., 1991) and its deficiency in mutant mice decreases the membrane bound spectrin concentration to about 1/2 normal (Bodine et al., 1984). A 70 kD internal domain of ankyrin extending from residue 828 to 898 and/or from residue 1101 to 1192 (Piatt et al., 1993) is critical for spectrin binding (Davis et al., 1990). Attachments between band 4.1 and both glycophorin C (Anderson and Lovrien, 1984) and the cytoplasmic domain of band 3 (Pasternack et al., 1985) stabilize the C3^oskeleton at the tail end. Glycophorin C levels in the cell appear to be dependent on the levels of band 4.1 (Reid et al., 1990) suggesting that protein 4.1 is required for glycophorin C membrane incorporation. This fact provides a putative explana tion for protein 4.rs role during spectrin nucleation to the membrane in late erythroblasts. Idenfification of band 3 binding sites for protein 4.1 includes an HTTSHP sequence within residues 1-201 at the amino terminus (Lombardo et al, 1992) and LRRRY/IRRRY sequences near the first transmembrane loop at residues 342-346 and 386-390, respectively (Jons and Drenckhahn, 1992). The band 4.1 site that binds to LRRRY/IRRRY is predicted to be the sequence LEEDY with opposite charge and identical hydrophobicity. LEEDY is present in the appropriate 4.1 amino terminal 30 kD domain known to bind band 3 (Leto and Marchesi, 1984). Interestingly, the hydrophobic sequence YRHKG in glycophorin C has the same charge distribution as LRRRY/IRRRY (Luna and Hitt, 1992). Interaction with excess ankyrin reduces 4.1 binding to the band 3 HTTSHP-inclusive region suggesting that band 4.1 and ankyrin may share a similar attachment site (Lombardo et al., 1992). Additional ankyrin binding sites on band 3 include the proline-rich hinge region encompassed by residues 174-190 (Davis and Bennett, 1989; Wil- lardsonetal, 1989) and Cys residues at 201 and317(Willardsonetal., 1989). Band 4.2 is an ankyrin binding protein that interacts with a unique site on band 3 and with band 4.1 (Korsgren and Cohen, 1988). The role of band 4.2 in the rbc membrane is not clear but it must influence rbc stability since its absence results in hemolytic anemia (Rybicki et al., 1988). Clearly, the membrane superstructure maintains the integrity of the rbc since deficiencies or aberrant structure of the cytoskeletal proteins cause hemolytic anemias of varying severity. The role of the proteins in disease was suspected, but not definitively confirmed, for almost 20 years after the discovery of spectrin in 1968 (Marchesi and Steers, 1968). Attempts to identify the molecular basis of the human hemolytic anemias has been abetted by the simultaneous and parallel investigations of animal models. In fact, the first clear demonstrafion that spectrin deficiency could be responsible for a heritable hemolytic anemia occurred in the mouse (Greenquist et al, 1978). The animal models continue to play a prominent role in the genetic and molecular dissection of heritable hemolytic anemia.
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