Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation.Librarian's Comment : Epididymosomes, which are small exosomal vesicles secreted by the epithelial cells of the epididymis, contain Wnt. Wnt is transferred to spermatozoa during epididymal transit. Usually Wnt signaling results in transcriptional activity via ß-catenin. However, in sperm transcription does not take place. Wnt signaling in sperm prevents degradation of numerous sperm proteins. Wnt action in sperm causes also inhibition of the important glycogen synthase kinase 3 (GSK3). GSK3 inhibition increases sperm motility. Addition of Wnt enhanced motility in human sperm obtained by TESE.
Published in : Cell
Authors : Koch S, Acebron SP, Herbst J, Hatiboglu G, Niehrs C
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 ß-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.