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Updated: Aug 15, 2026
In Vitro Cleavage Assays using Purified Recombinant Drosophila Caspases for Substrate Screening
Published on: October 6, 2022
Drosophila caspase transduces Shaggy/GSK-3beta kinase activity in neural precursor development
Hirotaka Kanuka1, Erina Kuranaga, Kiwamu Takemoto
1Department of Genetics, Graduate School of Pharmaceutical Sciences, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
Abstract:
Caspases are well known for their role in the execution of apoptotic programs, in which they cleave specific target proteins, leading to the elimination of cells, and for their role in cytokine maturation. In this study, we identified a novel substrate, which, through cleavage by caspases, can regulate Drosophila neural precursor development. Shaggy (Sgg)46 protein, an isoform encoded by the sgg gene and essential for the negative regulation of Wingless signaling, is cleaved by the Dark-dependent caspase. This cleavage converts it to an active kinase, which contributes to the formation of neural precursor (sensory organ precursor (SOP)) cells. Our evidence suggests that caspase regulation of the wingless pathway is not associated with apoptotic cell death. These results imply a novel role for caspases in modulating cell signaling pathways through substrate cleavage in neural precursor development.
Insights
Caspases cleave Shaggy (Sgg)46 protein, activating its kinase function. This regulates Drosophila neural precursor development, revealing a novel role for caspases in cell signaling beyond apoptosis.
Area of Science:
- Developmental Biology
- Cell Signaling
- Molecular Biology
Background:
- Caspases execute apoptosis by cleaving proteins and mature cytokines.
- Wingless signaling is crucial for development and negatively regulated by Shaggy (Sgg)46.
- Neural precursor development involves precise regulation of signaling pathways.
Purpose of the Study:
- To identify novel caspase substrates involved in Drosophila neural precursor development.
- To investigate the role of caspase-mediated cleavage of Shaggy (Sgg)46.
- To explore caspase function in cell signaling independent of apoptosis.
Main Methods:
- Identification of novel caspase substrates in Drosophila.
- Analysis of Shaggy (Sgg)46 protein cleavage by caspases.
- Assessment of the functional consequences of Sgg46 cleavage on neural precursor development.
Main Results:
- A novel caspase substrate, Shaggy (Sgg)46, was identified.
- Cleavage by the Dark-dependent caspase converts Sgg46 into an active kinase.
- This caspase-mediated activation of Sgg46 promotes the formation of sensory organ precursor (SOP) cells.
- Caspase regulation of Wingless signaling in this context is not linked to apoptotic cell death.
Conclusions:
- Caspases play a novel role in modulating cell signaling pathways during neural precursor development.
- Substrate cleavage by caspases can regulate developmental processes independently of apoptosis.
- The findings expand the understanding of caspase functions in biological regulation.
