The Zona Pellucida-Initiated Acrosome Reaction: Defect Due to Mutations in the Sperm Glycine Receptor/Cl− Channel
[摘要] Themammalianspermacrosomereaction(AR)isessentialtofertilization,andtheeggzonapellucida(ZP)isgenerallybelievedtobeaninvivoinitiatorofthefertilizingspermAR.Previouslyaneuronalglycinereceptor/Clminus;channel(GlyR)wasdetectedontheplasmamembraneofmammalianspermandearlierpharmacologicalstudiessuggestedthatthisreceptor/channelisimportanttotheZP-initiatedAR.Here,spermfrommicewithmutationsintheneuronalGlyRαorβsubunits(spasmodicandspastic)wereshowntobedeficientintheirabilitytoundergotheARinitiatedinvitrobyglycineorbysolubilizedZPfrommouseeggs.However,bothspontaneousandcalciumionophore(A23187)-initiatedARwereunaffected.TheZP-initiatedARinwild-typespermwasmaximalafter2hofcapacitation,butcapacitationofspermfromspasmodicmiceforupto3hdidnotresultinsignificantZP-initiatedAR.Similarresultswereobservedwhenspermfromwild-typeandspasticmicewerecompared.TestisfrommicewiththeβsubunitmutationcontainedtruncatedβsubunitmRNAs.Moreover,amonoclonalantibodyagainstGlyRcompletelyblockedZPinitiationofARinnormalmousesperm.OurresultsareconsistentwithanessentialroleforthespermGlyRintheZP-initiatedAR.
