FGFR-1 [corrected] signaling is involved in spermiogenesis and sperm capacitation.
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.
Cotton
Leanne
L
Monash Institute of Medical Research, Monash University, Melbourne, Australia.
Gibbs
Gerard M
GM
Sanchez-Partida
L Gabriel
LG
Morrison
John R
JR
de Kretser
David M
DM
O'Bryan
Moira K
MK
D000818:Animals; D005260:Female; D005298:Fertility / Q000502:physiology; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013075:Sperm Capacitation / Q000502:physiology*; D013091:Spermatogenesis / Q000502:physiology*; D013094:Spermatozoa / Q000166:cytology / Q000502:physiology; D019076:Transgenes
D016222:Fibroblast Growth Factor 2; D019869:Phosphatidylinositol 3-Kinases; D051496:Receptor, Fibroblast Growth Factor, Type 1; D020928:Mitogen-Activated Protein Kinases