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Published on: October 6, 2022
POSH misexpression induces caspase-dependent cell death in Drosophila
Ashley L Lennox1, Beth Stronach
1Department of Biological Sciences, 202 Life Sciences Annex, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
Abstract:
POSH (Plenty of SH3 domains) is a scaffold for signaling proteins regulating cell survival. Specifically, POSH promotes assembly of a complex including Rac GTPase, mixed lineage kinase (MLK), MKK7, and Jun kinase (JNK). In Drosophila, genetic analysis implicated POSH in Tak1-dependent innate immune response, in part through regulation of JNK signaling. Homologs of the POSH signaling complex components, MLK and MKK7, are essential in Drosophila embryonic dorsal closure. Using a gain-of-function approach, we tested whether POSH plays a role in this process. Ectopic expression of POSH in the embryo causes dorsal closure defects due to apoptosis of the amnioserosa, but ectodermal JNK signaling is normal. Phenotypic consequences of POSH expression were found to be dependent on Drosophila Nc, the caspase-9 homolog, but only partially on Tak1 and not at all on Slpr and Hep. These results suggest that POSH may use different signaling complexes to promote cell death in distinct contexts.
Insights
Plenty of SH3 domains (POSH) protein promotes cell death during Drosophila embryonic development. POSH expression causes developmental defects, suggesting its role in distinct signaling pathways.
Area of Science:
- Cellular signaling
- Developmental biology
- Apoptosis
Background:
- Plenty of SH3 domains (POSH) acts as a signaling scaffold, regulating cell survival pathways.
- POSH is known to assemble complexes involving Rac GTPase, mixed lineage kinase (MLK), MKK7, and Jun kinase (JNK).
- In Drosophila, POSH has been implicated in innate immunity via JNK signaling.
Purpose of the Study:
- To investigate the role of POSH in Drosophila embryonic dorsal closure.
- To determine if ectopic POSH expression affects embryonic development and associated signaling pathways.
Main Methods:
- Gain-of-function experiments using ectopic POSH expression in Drosophila embryos.
- Analysis of dorsal closure, apoptosis, and JNK signaling pathways.
- Genetic analysis of POSH-dependent phenotypes involving caspase-9 (Nc), Tak1, Slpr, and Hep.
Main Results:
- Ectopic POSH expression in Drosophila embryos resulted in dorsal closure defects.
- These defects were linked to apoptosis of the amnioserosa, while ectodermal JNK signaling remained normal.
- POSH-induced phenotypes were dependent on caspase-9 (Nc) and partially on Tak1, but not Slpr or Hep.
Conclusions:
- POSH plays a role in Drosophila embryonic development, specifically impacting dorsal closure through apoptosis.
- The signaling pathways utilized by POSH may differ depending on the cellular context.
- POSH might employ distinct signaling complexes to mediate cell death in various biological processes.
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