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Detecting Anastasis In Vivo by CaspaseTracker Biosensor
Published on: February 1, 2018
An atlas of caspase cleavage events in differentiating muscle cells
Erik Gomez-Cardona1, Mahshid H Dehkordi2, Kolden Van Baar1
1Department of Biochemistry, Faculty of Medicine and Dentistry, University of Alberta, Alberta, Canada.
Abstract:
Executioner caspases, such as caspase-3, are known to induce apoptosis, but in other contexts, they can control very different fates, including cell differentiation and neuronal plasticity. While hundreds of caspase substrates are known to be specifically targeted during cell death, we know very little about how caspase activity brings about non-apoptotic fates. Here, we report the first proteome identification of cleavage events in C2C12 cells undergoing myogenic differentiation and its comparison to undifferentiated or dying C2C12 cells. These data have identified new caspase substrates, including caspase substrates specifically associated with differentiation, and show that caspases are regulating proteins involved in myogenesis in myotubes, several days after caspase-3 initiated differentiation. Cytoskeletal proteins emerged as a major group of non-apoptotic caspase substrates. We also identified proteins with well-established roles in muscle differentiation as substrates cleaved in differentiating cells.
Insights
Caspases regulate cell differentiation beyond apoptosis. This study identifies new caspase substrates involved in muscle development, revealing their crucial role in myogenesis.
Area of Science:
- Cell Biology
- Biochemistry
- Molecular Biology
Background:
- Executioner caspases, like caspase-3, are primarily known for inducing apoptosis.
- However, caspases also regulate non-apoptotic cellular processes such as differentiation and plasticity.
- Understanding caspase substrates in non-apoptotic contexts is limited.
Purpose of the Study:
- To identify caspase cleavage events during myogenic differentiation in C2C12 cells.
- To compare these events with those in undifferentiated or dying cells.
- To uncover novel caspase substrates regulating non-apoptotic cell fates.
Main Methods:
- Proteomic analysis of C2C12 cells at different differentiation stages (undifferentiated, differentiating, dying).
- Mass spectrometry to identify cleaved peptides and thus caspase substrates.
- Comparative analysis of substrate profiles across conditions.
Main Results:
- Identification of a unique set of caspase substrates specifically cleaved during myogenic differentiation.
- Demonstration that caspases regulate proteins involved in myogenesis in myotubes.
- Cytoskeletal proteins identified as a major class of non-apoptotic caspase substrates.
- Proteins with established roles in muscle differentiation were found to be cleaved.
Conclusions:
- Caspase activity is critical for regulating non-apoptotic cell fates, including muscle differentiation.
- New caspase substrates involved in myogenesis have been identified.
- This work expands the known functions of caspases beyond cell death, highlighting their role in regulating complex cellular processes like differentiation.
