Trends in Cell Biology
ReviewDisassembly of the Dying: Mechanisms and Functions
Section snippets
Cell Disassembly as a Key Downstream Process of Apoptotic Cell Death
Billions of cells undergo apoptosis (a form of programmed cell death) daily as part of physiological homeostasis [1]. At later stages of apoptosis, some cell types can generate subcellular (1–5 μm) membrane-bound extracellular vesicles termed apoptotic bodies (ApoBDs, see Glossary) 1, 2, 3. ApoBDs are the largest type of extracellular vesicle compared to microparticles (50–1000 nm) and exosomes (30–100 nm) 2, 4, 5, 6 (Box 1). The formation of ApoBDs involves a series of morphological changes
Molecular Mechanisms of Apoptotic Cell Disassembly
The dismantling of an apoptotic cell into ApoBDs has been thought to be a stochastic process. However, recent studies suggest that the generation of ApoBDs is controlled by several well-coordinated morphological steps. The apoptotic cell disassembly process can be divided into three sequential steps governed by distinct morphological changes [1] (Figure 1). Step 1 describes the formation of plasma-membrane blebs on the cell surface. Particular cell types can then generate thin membrane
The Role of Apoptotic Cell Disassembly in Cell Clearance and Intercellular Communication
The formation of ApoBDs has been proposed to mediate two key functions: (i) to aid in the efficient removal of apoptotic cells, and (ii) to carry biomolecules such as nucleic acids and proteins to facilitate intercellular communication. We describe here the functions of apoptotic cell disassembly and the importance of this process in normal physiological and pathological conditions.
Concluding Remarks and Future Directions
It is becoming increasingly clear that apoptotic cell disassembly is a complex process, involving highly coordinated morphological steps. Depending on the mechanism used by a particular cell type to undergo apoptotic cell disassembly, a different quantity and quality of ApoBDs will be generated. These observations raise several unanswered questions as to why different cell types need to disassemble differently and the functional significance of such diversity (see Outstanding Questions).
Acknowledgments
We like to thank members of the laboratories of Mark Hulett and I.K.H.P. for discussions. This work was supported by Australian Postgraduate Awards to G.K.A-S and the La Trobe University Nicholas Hoogenraad Fellowship to I.K.H.P.
Glossary
- Actomyosin contraction
- a cellular process that describes the generation of contractile force though the interaction between filamentous actin and myosin II.
- Apoptotic body (ApoBD)
- a subcellular (1–5 μm diameter) extracellular vesicle generated from an apoptotic cell at the final stages of apoptotic cell disassembly.
- Apoptotic cell
- a cell that has begun apoptosis but has not undergone apoptotic cell disassembly.
- Apoptopodia
- string-like membrane protrusions found on apoptotic cells.
- Beaded apoptopodia
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