Acetylcholinesterase-R increases germ cell apoptosis but enhances sperm motility

Journal of Cellular and Molecular Medicine
Inbal MorHermona Soreq

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 sper...Continue Reading

References

May 1, 1991·Proceedings of the National Academy of Sciences of the United States of America·D Mochly-RosenJ Lopez
Nov 26, 1984·Biochimica Et Biophysica Acta·J A GrootegoedH J Van der Molen
Aug 1, 1980·International Journal of Andrology·G N Egbunike
Jul 13, 2000·Proceedings of the National Academy of Sciences of the United States of America·M SternfeldH Soreq
Aug 21, 2001·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·I MorH Soreq
Oct 19, 2001·Oncogene·D Schechtman, D Mochly-Rosen
Jan 31, 2002·Trends in Genetics : TIG·Annie YangFrank McKeon
Sep 26, 2002·Developmental Biology·Han-Chen HoSusan S Suarez
Nov 29, 2002·Human Reproduction·Branko ZornHelena Meden-Vrtovec
Jan 2, 2003·Proceedings of the National Academy of Sciences of the United States of America·Klara R BirikhHermona Soreq
Jan 30, 2003·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Talma BrennerHermona Soreq
Jul 1, 1961·Biochemical Pharmacology·G L ELLMANR M FEATHER-STONE
Oct 14, 2003·Biochemical Pharmacology·Upasna Gaur, Bharat B Aggarwal
Nov 18, 2004·Proceedings of the National Academy of Sciences of the United States of America·Kiyoshi MikiDeborah A O'Brien
Jul 20, 2005·Andrologia·S GrunewaldU Anderegg
Aug 3, 2005·Molecular Cell·Pablo López-BergamiZe'ev Ronai
Oct 4, 2005·Nature Reviews. Immunology·Kristin A HogquistStephen C Jameson
Nov 5, 2005·Chemico-biological Interactions·Brian C GeyerTsafrir S Mor
Dec 21, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Dan GrisaruVarda Deutsch
Feb 2, 2006·Genes & Development·Yael Gur, Haim Breitbart
Feb 7, 2006·Progress in Neurobiology·Ella H SklanHermona Soreq
Mar 7, 2006·Trends in Neurosciences·Eran Meshorer, Hermona Soreq

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Citations

Oct 8, 2011·Cell Communication and Signaling : CCS·David R AdamsPatrick A Kiely
Oct 3, 2012·PloS One·María-Salud García-AyllónJavier Sáez-Valero
Mar 27, 2010·Chemico-biological Interactions·Katarina PeganZoran Grubic
Jul 23, 2013·European Journal of Pharmacology·Edilson Dantas da Silva JúniorNeide Hyppolito Jurkiewicz
Jul 13, 2016·Archives of Insect Biochemistry and Physiology·Bin-Bin WangBing Li
Jun 13, 2012·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Kayo YoshimatsuMasahiro Nishijima
Feb 6, 2017·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·María Fernanda MontenegroCecilio J Vidal
Jan 11, 2019·International Journal of Environmental Research and Public Health·Xiuxia SongWei Yuan
Nov 11, 2009·Acta Biochimica Et Biophysica Sinica·Xiaowen GongXuejun Zhang

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Methods Mentioned

BETA
two-hybrid
co-immunoprecipitation
two hybrid
transgenic
electrophoresis
biopsies
PCR
Assay
transfections
motility measurements

Software Mentioned

Cell Quest
Swiss Model
ImagePro Plus
PatchDock
KALEIDAGRAPH
IVOS
Cell Quest Pro

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