Abstract
Tropomyosin and troponin have well known Ca2+-regulatory functions in the striated muscle sarcomere. In this review, we summarize experimental evidence that tropomyosin and troponin are localized, with as yet unidentified functional roles, in the striated muscle cell nucleus. We also apply bioinformatics approaches that predict localization of some tropomyosin and troponin to the nucleus, and that SUMOylation could be a covalent modification that modulates their nuclear localization and function. Further, we provide examples of cardiomyopathy mutations that alter the predicted likelihood of nuclear localization and SUMOylation of tropomyosin. These observations suggest novel mechanisms by which cardiomyopathy mutations in tropomyosin and troponin might alter not only cardiac contractility but also nuclear function.
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Notes
WoLF PSORT does not explicitly account for phosphorylation state or other covalent modifications of proteins in predictions of subcellular localization.
Protein sequences aligned with EMBL-EBI Clustal Omega Multiple Sequence Alignment using default parameters.
Protein sequences aligned with NCBI Cobalt Multiple Alignment Tool using default parameters (Papadopoulos and Agarwala 2007).
2′-Deoxyadenosine-5′-triphosphate (dATP) is the nucleotide that is incorporated into DNA and is missing a 2′ oxygen compared with adenosine-5′-triphosphate (ATP), which is the nucleotide that is incorporated into RNA and is the conventional substrate for actomyosin along with many other energy-requiring processes in cells.
Abbreviations
- cTn:
-
Cardiac troponin complex
- cTnC:
-
Cardiac troponin C
- cTnI:
-
Cardiac troponin I
- cTnT:
-
Cardiac troponin T
- dATP:
-
2′-Deoxyadenosine 5′-triphosphate
- PML bodies:
-
Nuclear promyelocytic leukemia protein bodies (nuclear dots)
- sTn:
-
Skeletal troponin complex
- sTnC:
-
Skeletal troponin C
- sTnI:
-
Skeletal troponin I
- sTnT:
-
Skeletal troponin T
- SUMO:
-
Small ubiquitin-like modifier protein
- SUMO1:
-
SUMO isoform 1
- SUMO2:
-
SUMO isoform 2
- SUMO3:
-
SUMO isoform 3
- Tm:
-
Tropomyosin
- Tn:
-
Troponin complex
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Acknowledgments
The authors are grateful to many colleagues at The Florida State University, and colleagues and collaborators from elsewhere, for thoughtful discussions. We especially thank Dr. Thomas C.S. Keller III, Dr. Campion K.P. Loong, Dr. Myriam A. Badr and Faizal Z. Asumda for insightful discussions, and Matthew S. Shachner for assistance with initial bioinformatics analyses.
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Submitted as a review for the special issue on ‘Tropomyosin: form and function,’ S. Marston and M, Gautel, eds.
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Chase, P.B., Szczypinski, M.P. & Soto, E.P. Nuclear tropomyosin and troponin in striated muscle: new roles in a new locale?. J Muscle Res Cell Motil 34, 275–284 (2013). https://doi.org/10.1007/s10974-013-9356-7
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DOI: https://doi.org/10.1007/s10974-013-9356-7