title: Molecular chaperones involved in protein degradation in the endoplasmic reticulum: quantitative interaction of the heat shock cognate protein BiP with partially folded immunoglobulin light chains that are degraded in the endoplasmic reticulum.
abstract: In the absence of immunoglobulin heavy-chain expression, some immunoglobulin light (L) chains are retained and degraded within the cell. We investigated the fate of two different nonsecreted murine L chains which exhibit different half-lives (50 min and 3-4 hr). Our results demonstrate that both nonsecreted L chains are quantitatively bound to BiP as partially oxidized molecules. The kinetics of L-chain degradation coincided with those of L-chain dissociation from BiP, which suggests that these two processes are functionally related. L-chain degradation does not depend on vesicular transport, indicating that these soluble proteins are degraded in the endoplasmic reticulum (ER). In contrast, secreted L chains, which interact only transiently with BiP, are completely oxidized and are not degraded even when they are artificially retained in the ER. Our data support the model that, by means of BiP interaction, the ER degradation mechanism has the potential to discriminate between partially and completely folded molecules.
authors.affiliation: Institute for Biochemistry I, University of Heidelberg, Germany.
authors.forename: M R
authors.initials: MR
authors.lastname: Knittler
authors.forename: S
authors.initials: S
authors.lastname: Dirks
authors.forename: I G
authors.initials: IG
authors.lastname: Haas
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007147:Immunoglobulin Light Chains / Q000378:metabolism*; D051379:Mice; D018832:Molecular Chaperones / Q000378:metabolism*; D008985:Monensin / Q000494:pharmacology; D010084:Oxidation-Reduction; D017510:Protein Folding; D013696:Temperature
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D006360:Heat-Shock Proteins; D007147:Immunoglobulin Light Chains; D018832:Molecular Chaperones; D008985:Monensin