6533b837fe1ef96bd12a203c

RESEARCH PRODUCT

Human peroxin PEX3 is co-translationally integrated into the ER and exits the ER in budding vesicles

Ismael MingarroPeter U. MayerhoferPeter U. MayerhoferPeter U. MayerhoferArthur E. JohnsonArthur E. JohnsonManuel Bañó-polo

subject

0301 basic medicineLipoproteinsPeroxinBiologyEndoplasmic ReticulumBiochemistryenvironment and public healthPeroxins03 medical and health sciencesStructural BiologyGeneticsPeroxisomesHumansMolecular BiologySignal recognition particle receptorAdaptor Proteins Signal TransducingSec61 transloconSignal recognition particlebudding vesiclesEndoplasmic reticulumCèl·lules eucarioteshuman peroxisomal membrane protein PEX3Proteïnes de membranaMembrane ProteinsCell BiologyOriginal ArticlesIntracellular MembranesTransloconSEC61 TransloconTransport proteinCell biologyperoxisomal biogenesisProtein Transport030104 developmental biologyMembrane proteinOriginal ArticleRibosomesSignal Recognition Particle

description

The long-standing paradigm that all peroxisomal proteins are imported post-translationally into pre-existing peroxisomes has been challenged by the detection of peroxisomal membrane proteins (PMPs) inside the endoplasmic reticulum (ER). In mammals, the mechanisms of ER entry and exit of PMPs are completely unknown. We show that the human PMP PEX3 inserts co-translationally into the mammalian ER via the Sec61 translocon. Photocrosslinking and fluorescence spectroscopy studies demonstrate that the N-terminal transmembrane segment (TMS) of ribosome-bound PEX3 is recognized by the signal recognition particle (SRP). Binding to SRP is a prerequisite for targeting of the PEX3-containing ribosome•nascent chain complex (RNC) to the translocon, where an ordered multistep pathway integrates the nascent chain into the membrane adjacent to translocon proteins Sec61α and TRAM. This insertion of PEX3 into the ER is physiologically relevant because PEX3 then exits the ER via budding vesicles in an ATP-dependent process. This study identifies early steps in human peroxisomal biogenesis by demonstrating sequential stages of PMP passage through the mammalian ER.

yearjournalcountryeditionlanguage
2015-12-01
10.1111/tra.12350https://doi.org/10.1111/tra.12350