Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility
| Autor: | Leticia Schreiber, Hermona Soreq, Inbal Mor, Tsafrir S. Mor, Brian C. Geyer, Ella H. Sklan, Erez Podoly, Dan Grisaru, Marjorie Pick, S. Bar-Sheshet Itach, Marc W. Kirschner, L. Yogev |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Biopsy Transgene Enolase Motility Mice Transgenic Biology Models Biological protein-protein interaction Mice Testis medicine Animals Humans Sperm motility apoptosis Articles acetylcholinesterase Cell Biology glycolysis Immunohistochemistry Spermatozoa Molecular biology Sperm spermatogenesis Cell biology Alternative Splicing medicine.anatomical_structure Apoptosis Sperm Motility Molecular Medicine Spermatogenesis Germ cell |
| Zdroj: | Journal of Cellular and Molecular Medicine |
| ISSN: | 1582-4934 1582-1838 |
| DOI: | 10.1111/j.1582-4934.2008.00231.x |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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