title: Protein disulfide isomerase-like proteins play opposing roles during retrotranslocation.
abstract: Misfolded proteins in the endoplasmic reticulum (ER) are retained in the organelle or retrotranslocated to the cytosol for proteasomal degradation. ER chaperones that guide these opposing processes are largely unknown. We developed a semipermeabilized cell system to study the retrotranslocation of cholera toxin (CT), a toxic agent that crosses the ER membrane to reach the cytosol during intoxication. We found that protein disulfide isomerase (PDI) facilitates CT retrotranslocation, whereas ERp72, a PDI-like protein, mediates its ER retention. In vitro analysis revealed that PDI and ERp72 alter CT's conformation in a manner consistent with their roles in retrotranslocation and ER retention. Moreover, we found that PDI's and ERp72's opposing functions operate on endogenous ER misfolded proteins. Thus, our data identify PDI family proteins that play opposing roles in ER quality control and establish an assay to further delineate the mechanism of CT retrotranslocation.
authors.affiliation: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, MI 48109, USA.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Forster
authors.forename: Kelsey
authors.initials: K
authors.lastname: Sivick
authors.forename: Young-Nam
authors.initials: YN
authors.lastname: Park
authors.forename: Peter
authors.initials: P
authors.lastname: Arvan
authors.forename: Wayne I
authors.initials: WI
authors.lastname: Lencer
authors.forename: Billy
authors.initials: B
authors.lastname: Tsai
mesh_terms: D018929:Cell Culture Techniques; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism; D015536:Down-Regulation; D004721:Endoplasmic Reticulum / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D006367:HeLa Cells; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology*; D019704:Protein Disulfide-Isomerases / Q000502:physiology*; D017510:Protein Folding; D021381:Protein Transport / Q000502:physiology*; D014734:Vibrio cholerae / Q000378:metabolism
chemical_list: D008562:Membrane Glycoproteins; C062477:endoplasmic reticulum glycoprotein p72; D002772:Cholera Toxin; D019704:Protein Disulfide-Isomerases