Alpha-tropomyosin mutations in inherited cardiomyopathies.
The inherited cardiac diseases hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be caused by missense mutations in the TPM1 gene which encodes the thin filament regulatory protein α-tropomyosin. Different mutations are responsible for either HCM or DCM, suggesting that dis...
| Main Authors: | , |
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| Format: | Journal article |
| Language: | English |
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2013
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| _version_ | 1826278807306240000 |
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| author | Redwood, C Robinson, P |
| author_facet | Redwood, C Robinson, P |
| author_sort | Redwood, C |
| collection | OXFORD |
| description | The inherited cardiac diseases hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be caused by missense mutations in the TPM1 gene which encodes the thin filament regulatory protein α-tropomyosin. Different mutations are responsible for either HCM or DCM, suggesting that distinct changes in tropomyosin structure and function can lead to the different diseases. Various biophysical and physiological approaches have been used to investigate the structure-function effects of the mutations, and animal models developed. The reported effects of the mutations include changes to the secondary structure of tropomyosin, its binding to actin and its position on the thin filament, and alterations to actin-myosin interactions and myofilament Ca(2+) sensitivity. The latter changes have been found to be particularly consistent, with HCM mutations increasing Ca(2+) sensitivity and DCM mutations in general decreasing this parameter and uncoupling the effect of troponin phosphorylation upon Ca(2+) responsiveness. As well as impacting on contractility, these changes are likely to alter intracellular Ca(2+) handling and signaling, and a combination of these alterations may provide the trigger for disease remodeling. |
| first_indexed | 2024-03-06T23:49:29Z |
| format | Journal article |
| id | oxford-uuid:7219e810-7aec-48d1-8398-7d945e90dffc |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-06T23:49:29Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:7219e810-7aec-48d1-8398-7d945e90dffc2022-03-26T19:47:59ZAlpha-tropomyosin mutations in inherited cardiomyopathies.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:7219e810-7aec-48d1-8398-7d945e90dffcEnglishSymplectic Elements at Oxford2013Redwood, CRobinson, PThe inherited cardiac diseases hypertrophic cardiomyopathy (HCM) and dilated cardiomyopathy (DCM) can both be caused by missense mutations in the TPM1 gene which encodes the thin filament regulatory protein α-tropomyosin. Different mutations are responsible for either HCM or DCM, suggesting that distinct changes in tropomyosin structure and function can lead to the different diseases. Various biophysical and physiological approaches have been used to investigate the structure-function effects of the mutations, and animal models developed. The reported effects of the mutations include changes to the secondary structure of tropomyosin, its binding to actin and its position on the thin filament, and alterations to actin-myosin interactions and myofilament Ca(2+) sensitivity. The latter changes have been found to be particularly consistent, with HCM mutations increasing Ca(2+) sensitivity and DCM mutations in general decreasing this parameter and uncoupling the effect of troponin phosphorylation upon Ca(2+) responsiveness. As well as impacting on contractility, these changes are likely to alter intracellular Ca(2+) handling and signaling, and a combination of these alterations may provide the trigger for disease remodeling. |
| spellingShingle | Redwood, C Robinson, P Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title | Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title_full | Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title_fullStr | Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title_full_unstemmed | Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title_short | Alpha-tropomyosin mutations in inherited cardiomyopathies. |
| title_sort | alpha tropomyosin mutations in inherited cardiomyopathies |
| work_keys_str_mv | AT redwoodc alphatropomyosinmutationsininheritedcardiomyopathies AT robinsonp alphatropomyosinmutationsininheritedcardiomyopathies |