Pro-apoptotic protein-protein interactions of the extended N-AChE terminus

Debra Toiber, David S. Greenberg, Hermona Soreq

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

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.

Original languageEnglish
Pages (from-to)1435-1442
Number of pages8
JournalJournal of Neural Transmission
Volume116
Issue number11
DOIs
StatePublished - 1 Nov 2009
Externally publishedYes

Keywords

  • Acetylcholinesterase
  • Apoptosis, N-AChE-S
  • Neurodegeneration
  • Protein-protein interactions

Fingerprint

Dive into the research topics of 'Pro-apoptotic protein-protein interactions of the extended N-AChE terminus'. Together they form a unique fingerprint.

Cite this