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.

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.

Related Concept Videos

Caspases01:24

Caspases

Caspase, a family of cysteine proteases, serve as effectors in apoptosis. The ced3 gene in C.elegans was first identified to be involved in apoptosis. This gene encodes the ced-3 caspase that is similar to the interleukin-1-beta converting enzyme or ICE in mammals. In addition to apoptosis, caspases also function in the inflammatory response. Inflammatory caspases are essential in activating pro-inflammatory cytokines that recruit immune cells and block the replication of pathogens inside cells.
Overview of Cell Death01:30

Overview of Cell Death

Cell death is an essential process where the body gets rid of old or damaged cells. Cell proliferation and death need to be balanced, as an imbalance between the two may lead to cancer or autoimmune diseases.
Cell death was observed in the early 19th century, but there was no experimental evidence to prove it. In 1842, Carl Vogt first discovered cell death in a metamorphic toad; however, it was not termed ‘cell death.’ Scientists discovered different cell death pathways only in the 20th century...
The Extrinsic Apoptotic Pathway01:17

The Extrinsic Apoptotic Pathway

The extrinsic apoptotic pathway is initiated when extracellular death-inducing signals, such as specific cytokines, activate the death receptors expressed on the cell surface. The immune cells involved in this pathway are natural killer cells (NK cells) and cytotoxic T-lymphocytes. NK cells are critical in innate immune response, while cytotoxic T-lymphocytes are associated with adaptive immune response. These cells recognize specific receptors expressed on the altered cells and activate...
The Intrinsic Apoptotic Pathway01:31

The Intrinsic Apoptotic Pathway

Internal cellular stress, such as cellular injury or hypoxia, triggers intrinsic apoptosis. The B-cell lymphoma 2 (Bcl-2) family of proteins are the primary regulators of the intrinsic apoptotic pathway. For example, during DNA damage, checkpoint proteins, such as Ataxia Telangiectasia Mutated (ATM protein) and Checkpoints Factor-2 (Chk2) proteins, are activated. These proteins phosphorylate p53 which further activates pro-apoptotic proteins, such as Bax, Bak, PUMA, and Noxa, and inhibits...
Apoptosis01:30

Apoptosis

Apoptosis is a combination of two Greek words, 'apo' and 'ptosis,' meaning separation and falling off, respectively. Hippocrates used this word to describe gangrene, which was caused due to bandaging of fractured bones. Apoptosis was distinguished from necrosis in 1970 when John Kerr reported observations of morphological changes occurring during apoptosis. During one experiment, he observed that the disruption of blood supply to the liver tissue resulted in a size reduction of the tissue.