Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility

I. Mor, E. H. Sklan, E. Podoly, M. Pick, M. Kirschner, L. Yogev, S. Bar-Sheshet Itach, L. Schreiber, B. Geyer, Tsafrir Leket-Mor, D. Grisaru, H. Soreq

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Changes in protein subdomains through alternative splicing often modify protein-protein interactions, altering biological processes. A relevant example is that of the stress-induced up-regulation of the acetylcholinesterase (AChE-R) splice variant, a common response in various tissues. In germ cells of male transgenic TgR mice, AChE-R excess associates with reduced sperm differentiation and sperm counts. To explore the mechanism(s) by which AChE-R up-regulation affects spermatogenesis, we identified AChE-R's protein partners through a yeast two-hybrid screen. In meiotic spermatocytes from TgR mice, we detected AChE-R interaction with the scaffold protein RACK1 and elevated apoptosis. This correlated with reduced scavenging by RACK1 of the pro-apoptotic TAp73, an outcome compatible with the increased apoptosis. In contrast, at later stages in sperm development, AChE-R's interaction with the glycolytic enzyme enolase-α elevates enolase activity. In transfected cells, enforced AChE-R excess increased glucose uptake and adenosine tri-phosphate (ATP) levels. Correspondingly, TgR sperm cells display elevated ATP levels, mitochondrial hyperactivity and increased motility. In human donors' sperm, we found direct association of sperm motility with AChE-R expression. Interchanging interactions with RACK1 and enolase-α may hence enable AChE-R to affect both sperm differentiation and function by participating in independent cellular pathways.

Original languageEnglish (US)
Pages (from-to)479-495
Number of pages17
JournalJournal of Cellular and Molecular Medicine
Volume12
Issue number2
DOIs
StatePublished - Apr 1 2008

    Fingerprint

Keywords

  • Acetylcholinesterase
  • Apoptosis
  • Glycolysis
  • Protein-protein interaction
  • Spermatogenesis

ASJC Scopus subject areas

  • Molecular Medicine
  • Cell Biology

Cite this

Mor, I., Sklan, E. H., Podoly, E., Pick, M., Kirschner, M., Yogev, L., Bar-Sheshet Itach, S., Schreiber, L., Geyer, B., Leket-Mor, T., Grisaru, D., & Soreq, H. (2008). Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. Journal of Cellular and Molecular Medicine, 12(2), 479-495. https://doi.org/10.1111/j.1582-4934.2008.00231.x