Calmodulin Mutations in Human Disease
ABSTRACTCalcium ions (Ca2+) are the basis of a unique and potent array of cellular responses. Calmodulin (CaM) is a small but vital protein that is able to rapidly transmit information about changes in Ca2+ concentrations to its regulatory targets. CaM plays a critical role in cellular Ca2+ signalin...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2023-12-01
|
| Series: | Channels |
| Subjects: | |
| Online Access: | https://www.tandfonline.com/doi/10.1080/19336950.2023.2165278 |
| _version_ | 1827631261838999552 |
|---|---|
| author | John W. Hussey Worawan B. Limpitikul Ivy E. Dick |
| author_facet | John W. Hussey Worawan B. Limpitikul Ivy E. Dick |
| author_sort | John W. Hussey |
| collection | DOAJ |
| description | ABSTRACTCalcium ions (Ca2+) are the basis of a unique and potent array of cellular responses. Calmodulin (CaM) is a small but vital protein that is able to rapidly transmit information about changes in Ca2+ concentrations to its regulatory targets. CaM plays a critical role in cellular Ca2+ signaling, and interacts with a myriad of target proteins. Ca2+-dependent modulation by CaM is a major component of a diverse array of processes, ranging from gene expression in neurons to the shaping of the cardiac action potential in heart cells. Furthermore, the protein sequence of CaM is highly evolutionarily conserved, and identical CaM proteins are encoded by three independent genes (CALM1-3) in humans. Mutations within any of these three genes may lead to severe cardiac deficits including severe long QT syndrome (LQTS) and/or catecholaminergic polymorphic ventricular tachycardia (CPVT). Research into disease-associated CaM variants has identified several proteins modulated by CaM that are likely to underlie the pathogenesis of these calmodulinopathies, including the cardiac L-type Ca2+ channel (LTCC) CaV1.2, and the sarcoplasmic reticulum Ca2+ release channel, ryanodine receptor 2 (RyR2). Here, we review the research that has been done to identify calmodulinopathic CaM mutations and evaluate the mechanisms underlying their role in disease. |
| first_indexed | 2024-03-09T14:18:31Z |
| format | Article |
| id | doaj.art-415c6b1ab79d4274b179828b8d19c980 |
| institution | Directory Open Access Journal |
| issn | 1933-6950 1933-6969 |
| language | English |
| last_indexed | 2024-03-09T14:18:31Z |
| publishDate | 2023-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Channels |
| spelling | doaj.art-415c6b1ab79d4274b179828b8d19c9802023-11-28T18:09:44ZengTaylor & Francis GroupChannels1933-69501933-69692023-12-0117110.1080/19336950.2023.2165278Calmodulin Mutations in Human DiseaseJohn W. Hussey0Worawan B. Limpitikul1Ivy E. Dick2Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USADepartment of Medicine, Division of Cardiology, Massachusetts General Hospital, Boston, MA, USADepartment of Physiology, University of Maryland School of Medicine, Baltimore, MD, USAABSTRACTCalcium ions (Ca2+) are the basis of a unique and potent array of cellular responses. Calmodulin (CaM) is a small but vital protein that is able to rapidly transmit information about changes in Ca2+ concentrations to its regulatory targets. CaM plays a critical role in cellular Ca2+ signaling, and interacts with a myriad of target proteins. Ca2+-dependent modulation by CaM is a major component of a diverse array of processes, ranging from gene expression in neurons to the shaping of the cardiac action potential in heart cells. Furthermore, the protein sequence of CaM is highly evolutionarily conserved, and identical CaM proteins are encoded by three independent genes (CALM1-3) in humans. Mutations within any of these three genes may lead to severe cardiac deficits including severe long QT syndrome (LQTS) and/or catecholaminergic polymorphic ventricular tachycardia (CPVT). Research into disease-associated CaM variants has identified several proteins modulated by CaM that are likely to underlie the pathogenesis of these calmodulinopathies, including the cardiac L-type Ca2+ channel (LTCC) CaV1.2, and the sarcoplasmic reticulum Ca2+ release channel, ryanodine receptor 2 (RyR2). Here, we review the research that has been done to identify calmodulinopathic CaM mutations and evaluate the mechanisms underlying their role in disease.https://www.tandfonline.com/doi/10.1080/19336950.2023.2165278Calmodulincalmodulinopathycardiac arrhythmiachannelopathylong QT syndrome |
| spellingShingle | John W. Hussey Worawan B. Limpitikul Ivy E. Dick Calmodulin Mutations in Human Disease Channels Calmodulin calmodulinopathy cardiac arrhythmia channelopathy long QT syndrome |
| title | Calmodulin Mutations in Human Disease |
| title_full | Calmodulin Mutations in Human Disease |
| title_fullStr | Calmodulin Mutations in Human Disease |
| title_full_unstemmed | Calmodulin Mutations in Human Disease |
| title_short | Calmodulin Mutations in Human Disease |
| title_sort | calmodulin mutations in human disease |
| topic | Calmodulin calmodulinopathy cardiac arrhythmia channelopathy long QT syndrome |
| url | https://www.tandfonline.com/doi/10.1080/19336950.2023.2165278 |
| work_keys_str_mv | AT johnwhussey calmodulinmutationsinhumandisease AT worawanblimpitikul calmodulinmutationsinhumandisease AT ivyedick calmodulinmutationsinhumandisease |