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西亚试剂:Cholesterol and the biosynthesis of glycosphingolipids are

Cholesterol and the biosynthesis of glycosphingolipids are required for spermactivation in Caenorhabditiselegans

Jiangli Dou, Lianwan Chen, Youqiao Hu, Long Miao,

 

Ejaculated mammalian sperm must acquire fertilization capacity after residing into the female reproductive tract, a process collectively known as capacitation. Cholesterol efflux was required for sperm maturation. Different from flagellated sperm, C. eleganssperm are crawling cells. C. eleganssperm are highly enriched with cholesterol though this animal species lacks biosynthetic pathway for cholesterol and its survival requires an exogenous cholesterol supply. The low abundance of cholesterol in C. elegans lipid extract is thought insufficient to form lipid microdomains ubiquitously in this organism. We present evidence that cholesterol is enriched in the plasma membrane of C. elegans spermatids and that cholesterol- and glycosphingolipids (GSLs)-enriched membrane microdomains (lipid microdomains) mediate spermactivation. Disruption of sperm lipid microdomains by acute manipulation of cholesterol in vitro blocks the spermactivation. Restriction of cholesterol uptake also results in the abnormal spermactivation in both males and hermaphrodites. Manipulation of the integrity of lipid microdomains by targeting the biosynthesis of GSLs inhibits spermactivation and the inhibition can be rescued by the addition of exogenous GSLs. The cleavage of glycosylphosphatidylinositol (GPI)-anchored proteins, which are exclusively found in lipid microdomains, also affects spermactivation. We conclude that localized signaling mediated by lipid microdomains is critical for worm spermactivation. Lipid microdomains composed of cholesterol and GSLs have been observed in flagellated sperm of several animal species, thus cholesterol, before its efflux from the plasma membrane, might be needed to assemble into a platform for some more important upstream signal sorting during spermatogenesis than was previously thought.