Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. Export

@article{citeulike:3814318, 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-alpha 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-alpha may hence enable AChE-R to affect both sperm differentiation and function by participating in independent cellular pathways.}, author = {Mor, I. and Sklan, E. H. and Podoly, E. and Pick, M. and Kirschner, M. and Yogev, L. and Bar-Sheshet Itach, S. and Schreiber, L. and Geyer, B. and Mor, T. and Grisaru, D. and Soreq, H.}, citeulike-article-id = {3814318}, citeulike-linkout-0 = {http://dx.doi.org/10.1111/j.1582-4934.2008.00231.x}, citeulike-linkout-1 = {http://view.ncbi.nlm.nih.gov/pubmed/18194455}, citeulike-linkout-2 = {http://www.hubmed.org/display.cgi?uids=18194455}, doi = {10.1111/j.1582-4934.2008.00231.x}, issn = {1582-1838}, journal = {Journal of cellular and molecular medicine}, keywords = {apoptosis, germcell, mouse, rack1}, month = {April}, number = {2}, pages = {479--495}, posted-at = {2008-12-20 09:58:07}, priority = {2}, title = {Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility.}, url = {http://dx.doi.org/10.1111/j.1582-4934.2008.00231.x}, volume = {12}, year = {2008} }

TY - JOUR ID - citeulike:3814318 L3 - citeulike-article-id:3814318 N2 - 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-alpha 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-alpha may hence enable AChE-R to affect both sperm differentiation and function by participating in independent cellular pathways. IS - 2 JF - Journal of cellular and molecular medicine SN - 1582-1838 EP - 495 TI - Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility. VL - 12 SP - 479 KW - apoptosis KW - germcell KW - mouse KW - rack1 AU - Mor, I AU - Sklan, EH AU - Podoly, E AU - Pick, M AU - Kirschner, M AU - Yogev, L AU - Bar-Sheshet Itach, S AU - Schreiber, L AU - Geyer, B AU - Mor, T AU - Grisaru, D AU - Soreq, H PY - 2008/04// UR - http://dx.doi.org/10.1111/j.1582-4934.2008.00231.x ER -