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Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Division of Molecular Embryology, DKFZ-ZMBH Alliance, Heidelberg, Germany.
Department of Urology, University of Heidelberg, Heidelberg, Germany.
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2015 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 163, no 5, 1225-1236 p.Article in journal (Refereed) Published
Abstract [en]

The canonical Wnt signaling pathway is of paramount importance in development and disease. An emergent question is whether the upstream cascade of the canonical Wnt pathway has physiologically relevant roles beyond beta-catenin-mediated transcription, which is difficult to study due to the pervasive role of this protein. Here, we show that transcriptionally silent spermatozoa respond to Wnt signals released from the epididymis and that mice mutant for the Wnt regulator Cyclin Y-like 1 are male sterile due to immotile and malformed spermatozoa. Post-transcriptional Wnt signaling impacts spermatozoa through GSK3 by (1) reducing global protein poly-ubiquitination to maintain protein homeostasis; (2) inhibiting septin 4 phosphorylation to establish a membrane diffusion barrier in the sperm tail; and (3) inhibiting protein phosphatase 1 to initiate sperm motility. The results indicate that Wnt signaling orchestrates a rich post-transcriptional sperm maturation program and invite revisiting transcription-independent Wnt signaling in somatic cells as well.

Place, publisher, year, edition, pages
Cambridge, United States: Cell Press , 2015. Vol. 163, no 5, 1225-1236 p.
Keyword [en]
Animals, Axin Protein/metabolism, Cyclins/metabolism, Epididymis/*metabolism, *Gene Expression Regulation, Glycogen Synthase Kinase 3/metabolism, Male, Mice, Phosphorylation, Protein Processing, Post-Translational, RNA Processing, Post-Transcriptional, Septins/metabolism, *Sperm Maturation, *Wnt Signaling Pathway
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Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:liu:diva-141656DOI: 10.1016/j.cell.2015.10.029ISI: 000366044700020PubMedID: 26590424Scopus ID: 2-s2.0-84947756267ISBN: 1097-4172 (Electronic) 0092-8674 (Linking) OAI: oai:DiVA.org:liu-141656DiVA: diva2:1149712
Note

Koch, Stefan Acebron, Sergio P Herbst, Jessica Hatiboglu, Gencay Niehrs, Christof eng Research Support, Non-U.S. Gov't 2015/11/23 06:00 Cell. 2015 Nov 19;163(5):1225-1236. doi: 10.1016/j.cell.2015.10.029.

Available from: 2017-10-16 Created: 2017-10-16 Last updated: 2017-10-25Bibliographically approved

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