Post-transcriptional Wnt Signaling Governs Epididymal Sperm Maturation

作者：Koch Stefan; Acebron Sergio P; Herbst Jessica; Hatiboglu Gencay; Niehrs Christof^*

来源：Cell, 2015, 163(5): 1225-1236.

DOI：10.1016/j.cell.2015.10.029

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 Upsilon-like 1 are male sterile due to immotile and malformed spermatozoa. Posttranscriptional 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.

• 出版日期2015-11-19