Aj. Travis et al., Functional relationships between capacitation-dependent cell signaling andcompartmentalized metabolic pathways in murine spermatozoa, J BIOL CHEM, 276(10), 2001, pp. 7630-7636
Spermatozoa are highly polarized cells with specific metabolic pathways com
partmentalized in different regions. Previously, we hypothesized that glyco
lysis is organized in the fibrous sheath of the flagellum to provide ATP to
dynein ATPases that generate motility and to protein kinases that regulate
motility. Although a recent report suggested that glucose is not essential
for murine sperm capacitation, we demonstrated that glucose (but not lacta
te or pyruvate) was necessary and sufficient to support the protein tyrosin
e phosphorylation events associated with capacitation. The effect of glucos
e on this signaling pathway was downstream of cAMP, and appeared to arise i
ndirectly as a consequence of metabolism as opposed to a direct signaling e
ffect Moreover, the phosphorylation events were not affected by uncouplers
of oxidative respiration, inhibitors of electron transfer, or by a lack of
substrates for oxidative respiration in the medium. Further experiments aim
ed,at identifying potential regulators of sperm,glycolysis focused on a ger
m cell-specific isoform of hexokinase, HK1-SC, which localizes to the fibro
us sheath. HK1-SC: activity and biochemical localization did not change dur
ing sperm capacitation, suggesting that glycolysis in sperm is regulated ei
ther at the level of substrate availability or by downstream enzymes. These
data Support the hypothesis that ATP specifically produced by a compartmen
talized glycolytic pathway in the principal piece of the flagellum, as oppo
sed to ATP generated by mitochondria in the mid-piece, is strictly required
for protein tyrosine phosphorylation events that take place during sperm c
apacitation. The relationship between these pathways suggests that spermato
zoa offer a model system for the study of integration of compartmentalized
metabolic and signaling pathways.