Division of labor among oxidoreductases: TMX1 preferentially acts on transmembrane polypeptides

Pisoni, G. B., Ruddock, L. W., Bulleid, N. and Molinari, M. (2015) Division of labor among oxidoreductases: TMX1 preferentially acts on transmembrane polypeptides. Molecular Biology of the Cell, 26(19), pp. 3390-3400. (doi:10.1091/mbc.E15-05-0321) (PMID:26246604) (PMCID:PMC4591685)

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Abstract

The endoplasmic reticulum (ER) is the site of maturation for secretory and membrane proteins in eukaryotic cells. The lumen of the mammalian ER contains >20 members of the protein disulfide isomerase (PDI) superfamily, which ensure formation of the correct set of intramolecular and intermolecular disulfide bonds as crucial, rate-limiting reactions of the protein folding process. Components of the PDI superfamily may also facilitate dislocation of misfolded polypeptides across the ER membrane for ER-associated degradation (ERAD). The reasons for the high redundancy of PDI family members and the substrate features required for preferential engagement of one or the other are poorly understood. Here we show that TMX1, one of the few transmembrane members of the family, forms functional complexes with the ER lectin calnexin and preferentially intervenes during maturation of cysteine-containing, membrane-associated proteins while ignoring the same cysteine-containing ectodomains if not anchored at the ER membrane. As such, TMX1 is the first example of a topology-specific client protein redox catalyst in living cells.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil
Authors: Pisoni, G. B., Ruddock, L. W., Bulleid, N., and Molinari, M.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Molecular Biology of the Cell
Publisher:American Society for Cell Biology
ISSN:1059-1524
ISSN (Online):1939-4586

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
528621Regulating the redox conditions within the mammalian endoplasmic reticulumNeil BulleidWellcome Trust (WELLCOME)088053/Z/08/ARI MOLECULAR CELL & SYSTEMS BIOLOGY