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In Vivo Biosensor Tracks Non-apoptotic Caspase Activity in Drosophila
Published on: November 27, 2016
Temporal regulation of Drosophila IAP1 determines caspase functions in sensory organ development
Akiko Koto1, Erina Kuranaga, Masayuki Miura
1Department of Genetics, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
The caspases comprise a family of cysteine proteases that function in various cellular processes, including apoptosis. However, how the balance is struck between the caspases' role in cell death and their nonapoptotic functions is unclear. To address this issue, we monitored the protein turnover of an endogenous caspase inhibitor, Drosophila IAP1 (DIAP1). DIAP1 is an E3 ubiquitin ligase that promotes the ubiquitination of caspases and thereby prevents caspase activation. For this study, we developed a fluorescent probe to monitor DIAP1 turnover in the external sensory organ precursor (SOP) lineage of living Drosophila. The SOP divides asymmetrically to make the shaft, socket, and sheath cells, and the neuron that comprise each sensory organ. We found that the quantity of DIAP1 changed dramatically depending on the cell type and maturity, and that the temporal regulation of DIAP1 turnover determines whether caspases function nonapoptotically in cellular morphogenesis or cause cell death.
Insights
Researchers tracked Drosophila IAP1 (DIAP1) protein levels in developing fruit flies. Temporal regulation of DIAP1 turnover dictates whether caspases promote cell death or nonapoptotic functions in cellular morphogenesis.
Area of Science:
- Cell Biology
- Developmental Biology
- Molecular Biology
Background:
- Caspases are cysteine proteases involved in apoptosis and other cellular processes.
- The balance between apoptotic and nonapoptotic caspase functions remains unclear.
- Drosophila IAP1 (DIAP1) is an E3 ubiquitin ligase that inhibits caspases by promoting their ubiquitination.
Purpose of the Study:
- To investigate the regulation of DIAP1 protein turnover.
- To understand how DIAP1 levels influence caspase activity in vivo.
- To determine the role of DIAP1 dynamics in balancing cell death and nonapoptotic functions.
Main Methods:
- Development of a fluorescent probe to monitor DIAP1 turnover in living Drosophila.
- Observation of DIAP1 dynamics in the external sensory organ precursor (SOP) lineage.
- Analysis of DIAP1 quantity changes in different cell types and developmental stages.
Main Results:
- DIAP1 quantity exhibited significant variations based on cell type and maturity.
- Temporal regulation of DIAP1 turnover was identified as a key factor.
- The study demonstrated a direct link between DIAP1 dynamics and caspase-mediated cell fate decisions.
Conclusions:
- DIAP1 protein turnover is dynamically regulated during Drosophila development.
- The precise control of DIAP1 levels is crucial for determining caspase function.
- This regulation governs whether caspases mediate cellular morphogenesis or induce apoptosis.

