Abstract
During apoptosis, cells undergo characteristic morphological changes in which the cytoskeleton plays an active role. The cytoskeleton rearrangements have been mainly attributed to actinomyosin ring contraction, while microtubule and intermediate filaments are depolymerized at early stages of apoptosis. However, recent results have shown that microtubules are reorganized during the execution phase of apoptosis forming an apoptotic microtubule network (AMN). Evidence suggests that AMN is required to maintain plasma membrane integrity and cell morphology during the execution phase of apoptosis. The new “two coffins” hypothesis proposes that both AMN and apoptotic cells can adopt two morphological patterns, round or irregular, which result from different cytoskeleton kinetic reorganization during the execution phase of apoptosis induced by genotoxic agents. In addition, round and irregular-shaped apoptosis showed different biological properties with respect to AMN maintenance, plasma membrane integrity and phagocyte responses. These findings suggest that knowing the type of apoptosis may be important to predict how fast apoptotic cells undergo secondary necrosis and the subsequent immune response. From a pathological point of view, round-shaped apoptosis can be seen as a physiological and controlled type of apoptosis, while irregular-shaped apoptosis can be considered as a pathological type of cell death closer to necrosis.
Highlights
An Overview of ApoptosisThe term “apoptosis” was coined by Kerr et al in the early 1970s to describe the ultrastructural features of dying cells seen during development of hepatocytes [1]
The influence of intermediate filaments (IF) proteins on the cytoskeleton reorganization kinetics that lead to round of irregular-shaped apoptosis has not been investigated yet, so this review will only focus on the current knowledge of the role of microtubules and actin filaments during apoptosis
As irregular-shaped apoptosis is dependent on early caspase activation, inhibition of caspases by z-VAD prevents both microtubules depolymerisation and ROCK1 and NET1 cleavage, allowing a slow actinomyosin ring contraction and, apoptotic cells adopt a round-shaped morphology [47]
Summary
The term “apoptosis” was coined by Kerr et al in the early 1970s to describe the ultrastructural features of dying cells seen during development of hepatocytes [1]. Efficient apoptotic cell removal is driven by the interaction with phagocytes through the expression of “eat-me” signals and the release of “find-me” signals, which facilitate the engulfment of the dying cell and its eventual digestion in their phagolysosomes. This process of apoptotic cell clearance is essential for tissue turnover and homeostasis [18]. This interaction prevents undesired immune reactions by contributing to the development of an immunomodulatory environment [19]
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