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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
09:18

Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death

Published on: December 27, 2016

Alix and ALG-2 are involved in tumor necrosis factor receptor 1-induced cell death

Anne-Laure Mahul-Mellier1, Flavie Strappazzon, Anne Petiot

  • 1INSERM, U836, Equipe 2, Neurodégénérescence et Plasticité, Grenoble F-38042, France.

The Journal of Biological Chemistry
|October 22, 2008
PubMed

Insights

Alix and ALG-2 proteins interact with TNF-R1 and caspase-8, regulating programmed cell death. This interaction is crucial for TNF-R1-induced neuronal death, highlighting Alix and ALG-2 as key pathway components.

Area of Science:

  • Cell Biology
  • Molecular Biology
  • Neuroscience

Background:

  • Alix/AIP1 is implicated in cell death pathways.
  • Alix interacts with ALG-2 and ESCRT proteins.
  • The role of Alix in TNF-R1 signaling is not fully understood.

Purpose of the Study:

  • To investigate the role of Alix and ALG-2 in TNF-R1-mediated cell death.
  • To identify proteins interacting with Alix in dying neurons.
  • To elucidate the mechanism of Alix and ALG-2 in regulating programmed cell death.

Main Methods:

  • Mass spectrometry to identify interacting proteins.
  • Co-immunoprecipitation to confirm protein interactions.
  • Functional assays using Alix mutants to assess cell death.

Main Results:

  • Caspase-8 was identified as a protein co-immunoprecipitating with Alix in dying neurons.
  • Alix and ALG-2 interact with pro-caspase-8 and form a complex with TNF-R1.
  • Alix-mediated recruitment of pro-caspase-8 to TNF-R1 containing endosomes is essential for TNF-R1-induced cell death.
  • Alix deleted of its ALG-2-binding site (AlixDeltaALG-2) significantly reduced TNF-R1-induced cell death and motoneuron death.

Conclusions:

  • Alix and ALG-2 are novel regulators of the TNF-R1 pathway.
  • Alix and ALG-2 facilitate the recruitment of pro-caspase-8 to TNF-R1 endosomes, promoting caspase activation and cell death.
  • Targeting Alix and ALG-2 may offer therapeutic strategies for conditions involving TNF-R1-mediated cell death.

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