Calmegin Is Required for Fertilin α/β Heterodimerization and Sperm Fertility

摘要

Lossoftheendoplasmicreticulumresidentchaperonecalmeginleadstotheproductionofsterilespermthatdonotbindtotheeggzonapellucida(M.Ikawaemetal.,/em1997,emNature/em387,607ndash;611).Inthepresentstudy,wedemonstratethatcalmeginminus;/minus;spermweredefectiveinmigratingintotheoviductsandinbindingtotheeggplasmamembrane.Despitetheimpairedadhesivefunction,calmeginminus;/minus;spermcouldfertilizeeggswhenzonaepellucidaewerepartiallydissected,andeggsfertilizedinthismannercoulddevelopnormallytoterm.Sincethesespermcharacteristicsweresimilartothosefoundinfertilinβminus;/minus;sperm,weinvestigatedtheinteractionofcalmeginwithfertilinβ.Usingimmunoprecipitationtechniques,calmeginwasfoundtobindtospermmembraneproteins,fertilinαandβ,duringspermatogenesis.Thebindingwasspecifictocalmegin:anotherendoplasmicreticulumchaperonecalnexin,acalmeginhomologue,wasnotabletobindtofertilinαandβ.Inthecalmeginminus;/minus;mice,alossofheterodimerizationoffertilinαandβwasobservedandfertilinβwasnotdetectableinmaturesperm.Thedatanotonlyexplainwhythecalmeginandfertilinβknockoutmouselinesshareacommoninfertilephenotype,butalsorevealtheimportanceofthematurationofspermmembraneproteinsintheendoplasmicreticulum./p/div