title: Misfolded endoplasmic reticulum retained subunits cause degradation of wild-type subunits of arylsulfatase A heteromers.
abstract: Arylsulfatase A is an oligomeric lysosomal enzyme. In the present study, we use this enzyme as a model protein to examine how heteromerization of wild-type and misfolded endoplasmic reticulum-degraded arylsulfatase A polypeptides affects the quality control of wild-type arylsulfatase A subunits. Using a conformation sensitive monoclonal antibody, we show that, within heteromers of misfolded and wild-type arylsulfatase A, the wild-type subunits are not fully folded. The results obtained show that arylsulfatase A polypeptide complexes, rather than the monomers, are subject to endoplasmic reticulum quality control and that, within a heteromer, the misfolded subunit exerts a dominant negative effect on the wild-type subunit. Although it has been shown that mature lysosomal arylsulfatase A forms dimers at neutral pH, the results obtained in the present study demonstrate that, in the early biosynthetic pathway, arylsulfatase A forms oligomers with more than two subunits.
authors.affiliation: Institut für Biochemie und Molekularbiologie, Rheinische-Friedrich-Wilhelms Universität Bonn, Bonn, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Poeppel
authors.forename: Mekky Mohamed
authors.initials: MM
authors.lastname: Abouzied
authors.forename: Christof
authors.initials: C
authors.lastname: Völker
authors.forename: Volkmar
authors.initials: V
authors.lastname: Gieselmann
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D002478:Cells, Cultured; D002553:Cerebroside-Sulfatase / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006224:Cricetinae; D019281:Dimerization; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation / Q000235:genetics; D017510:Protein Folding
chemical_list: D002553:Cerebroside-Sulfatase