title: Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation.
abstract: 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 β-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.
authors.affiliation: Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koch
authors.affiliation: Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Sergio P
authors.initials: SP
authors.lastname: Acebron
authors.affiliation: Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Herbst
authors.affiliation: Department of Urology, University of Heidelberg, 69120 Heidelberg, Germany.
authors.forename: Gencay
authors.initials: G
authors.lastname: Hatiboglu
authors.affiliation: Division of Molecular Embryology, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany; Institute of Molecular Biology (IMB), 55128 Mainz, Germany. Electronic address: niehrs@dkfz-heidelberg.de.
authors.forename: Christof
authors.initials: C
authors.lastname: Niehrs
mesh_terms: D000818:Animals; D060466:Axin Protein / Q000378:metabolism; D016213:Cyclins / Q000378:metabolism; D004822:Epididymis / Q000378:metabolism*; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D008297:Male; D051379:Mice; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012323:RNA Processing, Post-Transcriptional; D058112:Septins / Q000378:metabolism; D013079:Sperm Maturation; D060449:Wnt Signaling Pathway
chemical_list: D060466:Axin Protein; C555452:Axin1 protein, mouse; C000606102:Ccnyl1 protein, mouse; D016213:Cyclins; D038362:Glycogen Synthase Kinase 3; C115474:Sept4 protein, mouse; D058112:Septins