Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium
Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splic...
Main Authors: | , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Hindawi Limited
2010-01-01
|
Series: | Journal of Biomedicine and Biotechnology |
Online Access: | http://dx.doi.org/10.1155/2010/727239 |
id |
doaj-b40d6f83f3154bd3aac8356c314eaa08 |
---|---|
record_format |
Article |
spelling |
doaj-b40d6f83f3154bd3aac8356c314eaa082020-11-25T02:15:33ZengHindawi LimitedJournal of Biomedicine and Biotechnology1110-72431110-72512010-01-01201010.1155/2010/727239727239Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned MyocardiumHideto Fukushima0Charles S. Chung1Henk Granzier2Department of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, P.O. Box 245217, Tucson, AZ 85724, USADepartment of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, P.O. Box 245217, Tucson, AZ 85724, USADepartment of Physiology, Sarver Molecular Cardiovascular Research Program, University of Arizona, P.O. Box 245217, Tucson, AZ 85724, USATitin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a “viscous break” that is on during diastole and off during systole.http://dx.doi.org/10.1155/2010/727239 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Hideto Fukushima Charles S. Chung Henk Granzier |
spellingShingle |
Hideto Fukushima Charles S. Chung Henk Granzier Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium Journal of Biomedicine and Biotechnology |
author_facet |
Hideto Fukushima Charles S. Chung Henk Granzier |
author_sort |
Hideto Fukushima |
title |
Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium |
title_short |
Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium |
title_full |
Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium |
title_fullStr |
Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium |
title_full_unstemmed |
Titin-Isoform Dependence of Titin-Actin Interaction and Its Regulation by S100A1/Ca2+ in Skinned Myocardium |
title_sort |
titin-isoform dependence of titin-actin interaction and its regulation by s100a1/ca2+ in skinned myocardium |
publisher |
Hindawi Limited |
series |
Journal of Biomedicine and Biotechnology |
issn |
1110-7243 1110-7251 |
publishDate |
2010-01-01 |
description |
Titin, also known as connectin, is a large filamentous protein that greatly contributes to passive myocardial stiffness. In vitro evidence suggests that one of titin's spring elements, the PEVK, interacts with actin and that this adds a viscous component to passive stiffness. Differential splicing of titin gives rise to the stiff N2B and more compliant N2BA isoforms. Here we studied the titin-isoform dependence of titin-actin interaction and studied the bovine left atrium (BLA) that expresses mainly N2BA titin, and the bovine left ventricle (BLV) that expresses a mixture of both N2B and N2BA isforms. For comparison we also studied mouse left ventricular (MLV) myocardium which expresses predominately N2B titin. Using the actin-severing protein gelsolin, we obtained evidence that titin-actin interaction contributes significantly to passive myocardial stiffness in all tissue types, but most in MLV, least in BLA, and an intermediate level in BLV. We also studied whether titin-actin interaction is regulated by S100A1/calcium and found that calcium alone or S100A1 alone did not alter passive stiffness, but that combined they significantly lowered stiffness. We propose that titin-actin interaction is a “viscous break” that is on during diastole and off during systole. |
url |
http://dx.doi.org/10.1155/2010/727239 |
work_keys_str_mv |
AT hidetofukushima titinisoformdependenceoftitinactininteractionanditsregulationbys100a1ca2inskinnedmyocardium AT charlesschung titinisoformdependenceoftitinactininteractionanditsregulationbys100a1ca2inskinnedmyocardium AT henkgranzier titinisoformdependenceoftitinactininteractionanditsregulationbys100a1ca2inskinnedmyocardium |
_version_ |
1724895491242590208 |