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Article: Aberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease
Title | Aberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease |
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Authors | |
Issue Date | 2001 |
Publisher | American 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? |
Abstract | Schmid 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 Identifier | http://hdl.handle.net/10722/147468 |
ISSN | 2020 Impact Factor: 5.157 2023 SCImago Journal Rankings: 1.766 |
ISI Accession Number ID | |
References |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Chan, D | en_US |
dc.contributor.author | Ho, MSP | en_US |
dc.contributor.author | Cheah, KSE | en_US |
dc.date.accessioned | 2012-05-29T06:03:56Z | - |
dc.date.available | 2012-05-29T06:03:56Z | - |
dc.date.issued | 2001 | en_US |
dc.identifier.citation | Journal Of Biological Chemistry, 2001, v. 276 n. 11, p. 7992-7997 | en_US |
dc.identifier.issn | 0021-9258 | en_US |
dc.identifier.uri | http://hdl.handle.net/10722/147468 | - |
dc.description.abstract | Schmid 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.language | eng | en_US |
dc.publisher | American Society for Biochemistry and Molecular Biology, Inc. The Journal's web site is located at http://www.jbc.org/ | en_US |
dc.relation.ispartof | Journal of Biological Chemistry | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Bone Diseases - Genetics | en_US |
dc.subject.mesh | Collagen - Chemistry - Genetics - Metabolism | en_US |
dc.subject.mesh | Humans | en_US |
dc.subject.mesh | Mutation | en_US |
dc.subject.mesh | Protein Sorting Signals - Genetics | en_US |
dc.subject.mesh | Protein Structure, Secondary | en_US |
dc.subject.mesh | Rats | en_US |
dc.title | Aberrant signal peptide cleavage of collagen X in schmid metaphyseal chondrodysplasia. Implications for the molecular basis of the disease | en_US |
dc.type | Article | en_US |
dc.identifier.email | Chan, D:chand@hkucc.hku.hk | en_US |
dc.identifier.email | Cheah, KSE:hrmbdkc@hku.hk | en_US |
dc.identifier.authority | Chan, D=rp00540 | en_US |
dc.identifier.authority | Cheah, KSE=rp00342 | en_US |
dc.description.nature | link_to_OA_fulltext | en_US |
dc.identifier.doi | 10.1074/jbc.M003361200 | en_US |
dc.identifier.pmid | 11115494 | - |
dc.identifier.scopus | eid_2-s2.0-0035896588 | en_US |
dc.identifier.hkuros | 58487 | - |
dc.identifier.hkuros | 63694 | - |
dc.relation.references | http://www.scopus.com/mlt/select.url?eid=2-s2.0-0035896588&selection=ref&src=s&origin=recordpage | en_US |
dc.identifier.volume | 276 | en_US |
dc.identifier.issue | 11 | en_US |
dc.identifier.spage | 7992 | en_US |
dc.identifier.epage | 7997 | en_US |
dc.identifier.isi | WOS:000167474900046 | - |
dc.publisher.place | United States | en_US |
dc.identifier.scopusauthorid | Chan, D=7402216545 | en_US |
dc.identifier.scopusauthorid | Ho, MSP=7403080540 | en_US |
dc.identifier.scopusauthorid | Cheah, KSE=35387746200 | en_US |
dc.identifier.issnl | 0021-9258 | - |