FGRF-1 signaling is involved in spermiogenesis and sperm capacitation

• Published in: Journal of cell science Vol. 119; no. 1; pp. 75 - 84
• Main Authors: Cotton, Leanne, Gibbs, Gerard M, Sanchez-Partida, L. Gabriel, Morrison, John R, de Kretser, David M, O'Bryan, Moira K
• Format: Journal Article
• Language: English
• Published: 2006
• ISSN: 0021-9533; 1477-9137
• DOI: 10.1242/jcs.02704

Cloning of the fibroblast growth factor receptor (FGFR) adaptor Snt-2 cDNA and the identification of FGFR-1 protein in association with sperm tails, suggested that FGFR-1 signaling was involved in either sperm tail development or function. This hypothesis was tested by the creation of transgenic mice that specifically expressed a dominant-negative variant of FGFR-1 in male haploid germ cells. Mating of transgenic mice showed a significant reduction in pups per litter compared with wild-type littermates. Further analysis demonstrated that this subfertility was driven by a combination of reduced daily sperm output and a severely compromised ability of those sperm that were produced to undergo capacitation prior to fertilization. An analysis of key signal transduction proteins indicated that FGFR-1 is functional on wild-type sperm and probably signals via the phosphatidylinositol 3-kinase pathway. FGFR-1 activation also resulted in the downstream suppression of mitogen activated protein kinase signaling. These data demonstrate the FGFR-1 is required for quantitatively and qualitatively normal spermatogenesis and has a key role in the regulation of the global tyrosine phosphorylation events associated with sperm capacitation.