Keratin-mediated resistance to stress and apoptosis in simple epithelial cells in relation to health and disease

Citation
N. Marceau et al., Keratin-mediated resistance to stress and apoptosis in simple epithelial cells in relation to health and disease, BIOC CELL B, 79(5), 2001, pp. 543-555
Citations number
135
Language
INGLESE
art.tipo
Review
Categorie Soggetti
Cell & Developmental Biology
Journal title
BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE
ISSN journal
0829-8211 → ACNP
Volume
79
Issue
5
Year of publication
2001
Pages
543 - 555
Database
ISI
SICI code
0829-8211(200110)79:5<543:KRTSAA>2.0.ZU;2-0
Abstract
Epithelial cells such as hepatocytes exhibit highly polarized properties as a result of the asymmetric distribution of subsets of receptors at unique portions of the surface membrane. While the proper targeting of these surfa ce receptors and maintenance of the resulting polarity depend on microtubul es (MTs), the Golgi sorting compartment, and different actin-filament netwo rks, the contribution of keratin intermediate filaments (IFs) has been uncl ear. Recent data show that the latter cytoskeletal network plays a predomin ant role in providing resistance to various forms of stress and to apoptosi s targeted to the surface membrane. In this context, we first summarize our knowledge of the domain- or assembly-related features of IF proteins and t he dynamic properties of IF networks that may explain how the same keratin pair K8/K18 can exert multiple resistance-related functions in simple epith elial cells. We then examine the contribution of linker protein(s) that int egrate interactions of keratin IFs with MTs and the actin-cytoskeleton netw ork, polarity-dependent surface receptors and cytoplasmic organelles. We ne xt address likely molecular mechanisms by which K8/K18 can selectively prov ide resistance to a mechanical or toxic stress, or to Fas-mediated apoptosi s. Finally, these issues on keratin structure-function are examined within a context of pathological anomalies emerging in tissue architecture as a re sult of natural or targeted mutations, or posttranslational modifications a t specific amino acid residues. Clearly, the data accumulated in recent yea rs provide new and significant insights on the role of K8/K18, particularly under conditions where polarized cells resist to stressful or apoptotic in sults.