Uncovering the Roles of Intermediate Filaments in Apoptosis

• Published in: Methods in Cell Biology Vol. 78; pp. 95 - 129
• Main Authors: Marceau, Normand, Gilbert, Stéphane, Loranger, Anne
• Format: Book Chapter
• Language: English
• Published: Elsevier Science & Technology 2004
• ISBN: 0125641737; 9780125641739
• ISSN: 0091-679X
• DOI: 10.1016/S0091-679X(04)78005-X

Intermediate filament (IF) genes are differentially expressed according to cell lineage establishment and terminal cell differentiation, and in this context IF proteins constitute reliable sets of cell markers in normal tissues, except K8/K18 pair—the first cytoplasmic IF proteins to be expressed in the embryo. This chapter focuses on the analysis of the roles fulfilled by the events that provide cell resistance to apoptosis stimulation before commitment or those that are part of the execution phase in the committed cells. Although a prominent role for cytoskeleton is to maintain cellular integrity, it seems that IFs constitute a protein scaffold that is largely responsible for the capacity of cells to sustain mechanical and nonmechanical stresses including those that can lead to apoptosis. Because of their accessibility and their specialization—the availability of both tissue and primary culture based approaches and the severe IF-dependent diseases associated with them—keratinocytes and hepatocytes are the two cell models that are most frequently used, particularly to investigate IF involvement in cell stress and apoptosis under culture conditions. The chapter presents four main points on the role of IF: (1) IF proteins can readily be used as the markers of cell lineage establishment and cell differentiation, (2) apoptosis can occur by the stimulation of death receptors (DR) at the surface membrane or perturbation of mitochondria by toxic agents or oxidative stress, (3) the strongest experimental evidence for IF involvement in apoptosis has come from the work performed on simple epithelial cells, particularly for the K8/K18 pair, and (4) K8/K18 have been shown to be the modulators of apoptosis by acting both upstream and downstream of the caspase machinery activation.