Related Experiment Video
Updated: Jun 22, 2026

Strategies for Tracking Anastasis, A Cell Survival Phenomenon that Reverses Apoptosis
Published on: February 16, 2015
Pro-apoptotic protein-protein interactions of the extended N-AChE terminus
Debra Toiber1, David S Greenberg, Hermona Soreq
1Department of Biological Chemistry, The Hebrew University of Jerusalem, The Edmond J. Safra Campus, Jerusalem, Israel.
Abstract:
The N-terminally extended "synaptic" acetylcholinesterase variant N-AChE-S operates to promote apoptosis; however, the protein partners involved in this function remain unknown. Here, we report that when microinjected to fertilized mouse oocytes, N-AChE-S caused embryonic death as early as the zygotic stage. To identify the putative protein partners involved, we first tried yeast two hybrid screening, but this approach failed, probably because of the N-AChE-S-induced lethality. In contrast, sequence analysis and a corresponding peptide array revealed possible partners, which were validated by co-immunoprecipitation. These include the kinases GSK3, Aurora and GAK, the membrane integrin receptors, and the death receptor FAS. Each of these could potentially modulate N-AChE-S-induced apoptosis with possible therapeutic value for the treatment of Alzheimer's disease.
Insights
The synaptic acetylcholinesterase variant N-AChE-S induces embryonic death and apoptosis. Researchers identified its interacting partners, including kinases and receptors, offering potential Alzheimer's disease therapeutic targets.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- The N-terminally extended synaptic acetylcholinesterase variant (N-AChE-S) promotes apoptosis.
- Protein partners mediating N-AChE-S function are currently unknown.
Purpose of the Study:
- To identify protein partners interacting with N-AChE-S.
- To explore the role of these interactions in N-AChE-S-induced apoptosis and potential therapeutic applications.
Main Methods:
- Microinjection of N-AChE-S into fertilized mouse oocytes.
- Yeast two-hybrid screening (initially unsuccessful due to lethality).
- Peptide array analysis and co-immunoprecipitation for partner validation.
Main Results:
- N-AChE-S caused embryonic lethality at the zygotic stage in mouse oocytes.
- Identified interacting partners include kinases (GSK3, Aurora, GAK), integrin receptors, and the FAS death receptor.
- These interactions suggest modulation of N-AChE-S-induced apoptosis.
Conclusions:
- N-AChE-S interacts with key signaling proteins involved in apoptosis.
- These interactions may offer novel therapeutic strategies for Alzheimer's disease.
Related Concept Videos
The Intrinsic Apoptotic Pathway
The Extrinsic Apoptotic Pathway
Caspases
Apoptosis
Mitochondrial Precursor Proteins
Most of the mitochondrial precursors...
Phagocytosis of Apoptotic Cells
Normal cells contain receptors that prevent them from being recognized by phagocytes.

