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Article: Aberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease

TitleAberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease
Authors
Issue Date2001
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, 2001, v. 276 n. 11, p. 7992-7997 How to Cite?
AbstractSchmid metaphyseal chondrodysplasia results from mutations in the collagen X (COL10A1) gene. With the exception of two cases, the known mutations are clustered in the C-terminal nonhelical (NC1) domain of the collagen X. In vitro and cell culture studies have shown that the NC1 mutations result in impaired collagen X trimer assembly and secretion. In the two other cases, missense mutations that alter Gly18 at the -1 position of the putative signal peptide cleavage site were identified (Ikegawa, S., Nakamura, K., Nagano, A., Haga, N., and Nakamura, Y. (1997) Hum. Mutat. 9, 131-135). To study their impact on collagen X biosynthesis using in vitro cell-free translation in the presence of microsomes, and cell transfection assays, these two mutations were created in COL10A1 by site-directed mutagenesis. The data suggest that translocation of the mutant pre-α1(X) chains into the microsomes is not affected, but cleavage of the signal peptide is inhibited, and the mutant chains remain anchored to the membrane of microsomes. Cell-free translation and transfection studies in cells showed that the mutant chains associate into trimers but cannot form a triple helix. The combined effect of both the lack of signal peptide cleavage and helical configuration is impaired secretion. Thus, despite the different nature of the NC1 and signal peptide mutations in collagen X, both result in impaired collagen X secretion, probably followed by intracellular retention and degradation of mutant chains, and causing the Schmid metaphyseal chandrodysplasia phenotype.
Persistent Identifierhttp://hdl.handle.net/10722/147468
ISSN
2015 Impact Factor: 4.258
2015 SCImago Journal Rankings: 3.151
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorChan, Den_US
dc.contributor.authorHo, MSPen_US
dc.contributor.authorCheah, KSEen_US
dc.date.accessioned2012-05-29T06:03:56Z-
dc.date.available2012-05-29T06:03:56Z-
dc.date.issued2001en_US
dc.identifier.citationJournal Of Biological Chemistry, 2001, v. 276 n. 11, p. 7992-7997en_US
dc.identifier.issn0021-9258en_US
dc.identifier.urihttp://hdl.handle.net/10722/147468-
dc.description.abstractSchmid metaphyseal chondrodysplasia results from mutations in the collagen X (COL10A1) gene. With the exception of two cases, the known mutations are clustered in the C-terminal nonhelical (NC1) domain of the collagen X. In vitro and cell culture studies have shown that the NC1 mutations result in impaired collagen X trimer assembly and secretion. In the two other cases, missense mutations that alter Gly18 at the -1 position of the putative signal peptide cleavage site were identified (Ikegawa, S., Nakamura, K., Nagano, A., Haga, N., and Nakamura, Y. (1997) Hum. Mutat. 9, 131-135). To study their impact on collagen X biosynthesis using in vitro cell-free translation in the presence of microsomes, and cell transfection assays, these two mutations were created in COL10A1 by site-directed mutagenesis. The data suggest that translocation of the mutant pre-α1(X) chains into the microsomes is not affected, but cleavage of the signal peptide is inhibited, and the mutant chains remain anchored to the membrane of microsomes. Cell-free translation and transfection studies in cells showed that the mutant chains associate into trimers but cannot form a triple helix. The combined effect of both the lack of signal peptide cleavage and helical configuration is impaired secretion. Thus, despite the different nature of the NC1 and signal peptide mutations in collagen X, both result in impaired collagen X secretion, probably followed by intracellular retention and degradation of mutant chains, and causing the Schmid metaphyseal chandrodysplasia phenotype.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.meshAnimalsen_US
dc.subject.meshBone Diseases - Geneticsen_US
dc.subject.meshCollagen - Chemistry - Genetics - Metabolismen_US
dc.subject.meshHumansen_US
dc.subject.meshMutationen_US
dc.subject.meshProtein Sorting Signals - Geneticsen_US
dc.subject.meshProtein Structure, Secondaryen_US
dc.subject.meshRatsen_US
dc.titleAberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the diseaseen_US
dc.typeArticleen_US
dc.identifier.emailChan, D:chand@hkucc.hku.hken_US
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_US
dc.identifier.authorityChan, D=rp00540en_US
dc.identifier.authorityCheah, KSE=rp00342en_US
dc.description.naturelink_to_OA_fulltexten_US
dc.identifier.doi10.1074/jbc.M003361200en_US
dc.identifier.pmid11115494-
dc.identifier.scopuseid_2-s2.0-0035896588en_US
dc.identifier.hkuros58487-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0035896588&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume276en_US
dc.identifier.issue11en_US
dc.identifier.spage7992en_US
dc.identifier.epage7997en_US
dc.identifier.isiWOS:000167474900046-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridChan, D=7402216545en_US
dc.identifier.scopusauthoridHo, MSP=7403080540en_US
dc.identifier.scopusauthoridCheah, KSE=35387746200en_US

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