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Article: Endoplasmic reticulum-mediated quality control of type I collagen production by cells from osteogenesis imperfecta patients with mutations in the proα1(I) chain carboxyl-terminal propeptide which impair subunit assembly

TitleEndoplasmic reticulum-mediated quality control of type I collagen production by cells from osteogenesis imperfecta patients with mutations in the proα1(I) chain carboxyl-terminal propeptide which impair subunit assembly
Authors
Issue Date1995
PublisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/
Citation
Journal Of Biological Chemistry, 1995, v. 270 n. 15, p. 8642-8649 How to Cite?
AbstractA heterozygous single base change in exon 49 of COL1A1, which converted the codon for proα1(I) carboxyl-terminal propeptide residue 94 from tryptophan (TGG) to cysteine (TGT) was identified in a baby with lethal osteogenesis imperfecta (OI64). The C-propeptide mutations in OI64 and in another lethal osteogenesis imperfecta cell strain (OI26), which has a frameshift mutation altering the sequence of the carboxyl-terminal half of the propeptide (Bateman, J. F., Lamande, S. R., Dahl, H.-H. M., Chan, D., Mascara, T. and Cole, W. G. (1989) J. Biol. Chem. 264, 10960-10964), disturbed procollagen folding and retarded the formation of disulfide- linked trimers. Although assembly was delayed, the presence of slowly migrating, overmodified α1(I) and α2(I) chains indicated that mutant proα1(I) could associate with normal proα1(I) and proα2(I) to form pepsin-resistant triple-helical molecules, a proportion of which were secreted. Further evidence of the aberrant folding of mutant procollagen in OI64 and OI26 was provided by experiments demonstrating that the endoplasmic reticulum resident molecular chaperone BiP, which binds to malfolded proteins, was specifically bound to type I procollagen and was coimmunoprecipitated in the osteogenesis imperfecta cells but not control cells. Experiments with brefeldin A, which inhibits protein export from the endoplasmic reticulum, demonstrated that unassembled mutant proα1(I) chains were selectively degraded within the endoplasmic reticulum resulting in reduced collagen production by the osteogenesis imperfecta cells. This biosynthetic deficiency was reflected in the inability of OI64 and OI26 cells to produce a substantial in vitro collagenous matrix when grown in the continuous presence of ascorbic acid to allow collagen matrix formation. Both these carboxyl-terminal propeptide mutants showed a marked reduction in collagen accumulation to 20% (or less) of control cultures, comparable to the reduced collagen content of tissues from OI26.
Persistent Identifierhttp://hdl.handle.net/10722/147393
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLamande, SRen_US
dc.contributor.authorChessler, SDen_US
dc.contributor.authorGolub, SBen_US
dc.contributor.authorByers, PHen_US
dc.contributor.authorChan, Den_US
dc.contributor.authorCole, WGen_US
dc.contributor.authorSillence, DOen_US
dc.contributor.authorBateman, JFen_US
dc.date.accessioned2012-05-29T06:03:24Z-
dc.date.available2012-05-29T06:03:24Z-
dc.date.issued1995en_US
dc.identifier.citationJournal Of Biological Chemistry, 1995, v. 270 n. 15, p. 8642-8649en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/147393-
dc.description.abstractA heterozygous single base change in exon 49 of COL1A1, which converted the codon for proα1(I) carboxyl-terminal propeptide residue 94 from tryptophan (TGG) to cysteine (TGT) was identified in a baby with lethal osteogenesis imperfecta (OI64). The C-propeptide mutations in OI64 and in another lethal osteogenesis imperfecta cell strain (OI26), which has a frameshift mutation altering the sequence of the carboxyl-terminal half of the propeptide (Bateman, J. F., Lamande, S. R., Dahl, H.-H. M., Chan, D., Mascara, T. and Cole, W. G. (1989) J. Biol. Chem. 264, 10960-10964), disturbed procollagen folding and retarded the formation of disulfide- linked trimers. Although assembly was delayed, the presence of slowly migrating, overmodified α1(I) and α2(I) chains indicated that mutant proα1(I) could associate with normal proα1(I) and proα2(I) to form pepsin-resistant triple-helical molecules, a proportion of which were secreted. Further evidence of the aberrant folding of mutant procollagen in OI64 and OI26 was provided by experiments demonstrating that the endoplasmic reticulum resident molecular chaperone BiP, which binds to malfolded proteins, was specifically bound to type I procollagen and was coimmunoprecipitated in the osteogenesis imperfecta cells but not control cells. Experiments with brefeldin A, which inhibits protein export from the endoplasmic reticulum, demonstrated that unassembled mutant proα1(I) chains were selectively degraded within the endoplasmic reticulum resulting in reduced collagen production by the osteogenesis imperfecta cells. This biosynthetic deficiency was reflected in the inability of OI64 and OI26 cells to produce a substantial in vitro collagenous matrix when grown in the continuous presence of ascorbic acid to allow collagen matrix formation. Both these carboxyl-terminal propeptide mutants showed a marked reduction in collagen accumulation to 20% (or less) of control cultures, comparable to the reduced collagen content of tissues from OI26.en_US
dc.languageengen_US
dc.publisherAmerican Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/en_US
dc.relation.ispartofJournal of Biological Chemistryen_US
dc.subject.meshBase Sequenceen_US
dc.subject.meshBrefeldin Aen_US
dc.subject.meshCarrier Proteins - Metabolismen_US
dc.subject.meshCells, Cultureden_US
dc.subject.meshCollagen - Biosynthesis - Geneticsen_US
dc.subject.meshCyclopentanes - Pharmacologyen_US
dc.subject.meshDna Primersen_US
dc.subject.meshDisulfides - Metabolismen_US
dc.subject.meshEndoplasmic Reticulum - Metabolismen_US
dc.subject.meshFibroblasts - Metabolismen_US
dc.subject.meshHeat-Shock Proteinsen_US
dc.subject.meshHumansen_US
dc.subject.meshInfant, Newbornen_US
dc.subject.meshMolecular Chaperones - Metabolismen_US
dc.subject.meshMolecular Sequence Dataen_US
dc.subject.meshMutationen_US
dc.subject.meshOsteogenesis Imperfecta - Genetics - Metabolismen_US
dc.subject.meshPrecipitin Testsen_US
dc.subject.meshProcollagen - Genetics - Metabolismen_US
dc.subject.meshRna, Messenger - Geneticsen_US
dc.titleEndoplasmic reticulum-mediated quality control of type I collagen production by cells from osteogenesis imperfecta patients with mutations in the proα1(I) chain carboxyl-terminal propeptide which impair subunit assemblyen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1074/jbc.270.15.8642en_US
dc.identifier.pmid7721766en_US
dc.identifier.scopuseid_2-s2.0-0028902639en_US
dc.identifier.volume270en_US
dc.identifier.issue15en_US
dc.identifier.spage8642en_US
dc.identifier.epage8649en_US
dc.identifier.isiWOS:A1995QT44800043-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLamande, SR=7004500719en_US
dc.identifier.scopusauthoridChessler, SD=6602083095en_US
dc.identifier.scopusauthoridGolub, SB=35609444800en_US
dc.identifier.scopusauthoridByers, PH=7102745602en_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridCole, WG=7201518727en_US
dc.identifier.scopusauthoridSillence, DO=7006527427en_US
dc.identifier.scopusauthoridBateman, JF=16135557700en_US

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