Caspases help to spread the message via extracellular vesicles

Abstract

Cell‐cell communication is an essential aspect of multicellular life, key for coordinating cell proliferation, growth, and death in response to environmental changes. Whilst caspases are well‐known for facilitating apoptotic and pyroptotic cell death, several recent investigations are uncovering new roles for these enzymes in biological scenarios requiring long‐range intercellular signalling mediated by extracellular vesicles (EVs). EVs are small membrane‐bound nanoparticles released from cells that may carry and deliver cargo between distant cells, thus helping to coordinate their behaviour. Intriguingly, there is emerging evidence indicating a key contribution of caspases in the biogenesis of EVs, the selection of their cargo content, and EV uptake/function in recipient cells. Here, we discuss the latest findings supporting the interplay between caspases and EVs, and the biological relevance of this molecular convergence for cellular signalling, principally in non‐apoptotic scenarios.

Uncovering the bequeathing potential of Apoptotic Mesenchymal Stem Cells via small Extracellular Vesicles for its enhanced immunomodulatory ability

“…Annexin/PI staining was used to assess the percentage of cumulative apoptotic cells which was 99.45% (53.37% early & 46.08% late apoptotic cells) and 99.60% (52.50% early & 47.10% late apoptotic cells) at a 12h time point in BM-MSCs & WJ-MSCs respectively, whereas at 24h there was a decline in the number of apoptotic cells in both the groups (99.30% and 89.28% respectively) (Figure 1B, C). Furthermore, at this time point, the cells displayed the hallmark features of apoptosis induction including significant morphological alteration, cell blebbing, and shrinkage [26] (Figure 1A). Induction of apoptosis was also validated via western blotting in both the tissue-specific MSCs in terms of the Caspase 3 expression (Figure S2).…”

“…Caspase-3 has been found to cleave Rho-associated protein kinase (ROCK I), which leads to the remodelling of actin and microtubules present at the plasma membrane, therefore resulting in membrane blebbing and EV formation. However, the precise mechanism for the heightened secretion remains unclear [26,30].…”

Similar but distinct: The impact of biomechanical forces and culture age on the production, cargo loading, and biological efficacy of human megakaryocytic extracellular vesicles for applications in cell and gene therapies

“…We have previously discovered that nonapoptotic caspase action mediates the increased release of large MkEVs under very low levels of shear stress 13 . Such caspase activity is commonly implicated in the biogenesis of other EVs, 64 and may provide a fruitful starting point for future investigations into MkEV cargo loading specifically. Figure 11 illustrates common mechanisms by which biomechanical force mediates EV biology, providing additional avenues of inquiry for future MkEV research 25…”

Hijacking homeostasis: Regulation of the tumor microenvironment by apoptosis

“…Related to this, failed apoptosis and nonapoptotic functions of the apoptosis machinery have implications for tumor emergence and progression (reviewed in 288–290 ). Non‐canonical functions of caspases, for example, may be important in driving proliferation 291 and EV biogenesis and activities 292 . In Drosophila , it was found that translocation of the initiator caspase, Dronc to the plasma membrane by the unconventional myosin, Myo1D can activate AiP‐like proliferation, independently of apoptosis through activation of the fly NADPH oxidase, Duox which generates reactive oxygen species 293 .…”