Protein disulfide isomerase activity is essential for viability and extracellular matrix formation in the nematode Caenorhabditis elegans

摘要

Proteindisulfideisomerase(PDI)isamultifunctionalproteinrequiredformanyaspectsofproteinfoldingandtransitthroughtheendoplasmicreticulum.AconservedfamilyofthreePDIshasbeenfunctionallyanalysedusinggeneticmutantsofthemodelorganismemCaenorhabditiselegans/em.PDI-1andPDI-3areindividuallynon-essential,whereasPDI-2isrequiredfornormalpost-embryonicdevelopment.Incombination,allthreegenesaresynergisticallyessentialforembryonicdevelopmentinthisnematode.Mutationsinempdi-2/emresultinseverebodymorphologydefects,uncoordinatedmovement,adultsterility,abnormalmoltingandaberrantcollagendeposition.Manyofthesephenotypesareconsistentwitharoleincollagenbiogenesisandextracellularmatrixformation.PDI-2isrequiredforthenormalfunctionofprolyl4-hydroxylase,akeycollagen-modifyingenzyme.Site-directedmutagenesisindicatesthattheindependentcatalyticactivityofPDI-2mayalsoperformanessentialdevelopmentalfunction.PDI-2thereforeperformstwocriticalrolesduringmorphogenesis.TheroleofPDI-2incollagenbiogenesiscanberestoredfollowingcomplementationofthemutantwithhumanPDI./p/div