The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin
Striated muscle contraction is regulated by the actin binding proteins tropomyosin and troponin. Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated acti...
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| Veröffentlicht in: | Biophysical journal 2012-06, Vol.102 (11), p.2536-2544 |
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| description | Striated muscle contraction is regulated by the actin binding proteins tropomyosin and troponin. Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated actin containing Δ14 TnT was more readily activated than wild-type regulated actin. We suggested that the equilibria among the inactive (blocked), intermediate (closed or calcium), and active (open or myosin) states was shifted to the active state. We now show that, in addition, such regulated actin filaments cannot enter the inactive or blocked state. Regulated actin containing Δ14 TnT had ATPase activities in the absence of Ca2+ that were higher than wild-type filaments but far below the fully active rate. The rapid dissociation of S1-ATP from regulated actin filaments containing Δ14 TnT and acrylodan-labeled tropomyosin did not show the fluorescence increase characteristic of moving to the inactive state. Replacing wild-type TnI with S45E TnI, that favors the inactive state, did not restore the fluorescence change. We conclude that TnT has a previously unrecognized role in forming the inactive state of regulated actin. |
| doi_str_mv | 10.1016/j.bpj.2012.04.037 |
| format | Article |
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Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated actin containing Δ14 TnT was more readily activated than wild-type regulated actin. We suggested that the equilibria among the inactive (blocked), intermediate (closed or calcium), and active (open or myosin) states was shifted to the active state. We now show that, in addition, such regulated actin filaments cannot enter the inactive or blocked state. Regulated actin containing Δ14 TnT had ATPase activities in the absence of Ca2+ that were higher than wild-type filaments but far below the fully active rate. The rapid dissociation of S1-ATP from regulated actin filaments containing Δ14 TnT and acrylodan-labeled tropomyosin did not show the fluorescence increase characteristic of moving to the inactive state. Replacing wild-type TnI with S45E TnI, that favors the inactive state, did not restore the fluorescence change. We conclude that TnT has a previously unrecognized role in forming the inactive state of regulated actin.</description><identifier>ISSN: 0006-3495</identifier><identifier>EISSN: 1542-0086</identifier><identifier>DOI: 10.1016/j.bpj.2012.04.037</identifier><identifier>PMID: 22713569</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>2-Naphthylamine - analogs & derivatives ; 2-Naphthylamine - metabolism ; actin ; Actins - metabolism ; Adenosine triphosphatase ; Adenosine Triphosphate - metabolism ; adenosinetriphosphatase ; Animals ; Calcium ; Calcium - pharmacology ; cardiomyopathy ; dissociation ; Ethylmaleimide - pharmacology ; Fluorescence ; Humans ; Kinetics ; Light ; microfilaments ; Models, Biological ; muscle contraction ; Muscle, Motility, and Motor Proteins ; Muscle, Skeletal - enzymology ; muscular diseases ; Mutant Proteins - metabolism ; myosin ; Myosins - metabolism ; Proteins ; Scattering, Radiation ; striated muscle ; Structure-Activity Relationship ; Time Factors ; Tropomyosin - metabolism ; tropomyosins ; troponin T ; Troponin T - chemistry ; Troponin T - metabolism</subject><ispartof>Biophysical journal, 2012-06, Vol.102 (11), p.2536-2544</ispartof><rights>2012 Biophysical Society</rights><rights>Copyright © 2012 Biophysical Society. Published by Elsevier Inc. All rights reserved.</rights><rights>Copyright Biophysical Society Jun 6, 2012</rights><rights>2012 by the Biophysical Society. 2012 Biophysical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c503t-773c8521d4539df8214cd74a9b2817e52f06e9087bc8235d58a0a22ede20cc4b3</citedby><cites>FETCH-LOGICAL-c503t-773c8521d4539df8214cd74a9b2817e52f06e9087bc8235d58a0a22ede20cc4b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3368147/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bpj.2012.04.037$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22713569$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Franklin, Andrew J.</creatorcontrib><creatorcontrib>Baxley, Tamatha</creatorcontrib><creatorcontrib>Kobayashi, Tomoyoshi</creatorcontrib><creatorcontrib>Chalovich, Joseph M.</creatorcontrib><title>The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin</title><title>Biophysical journal</title><addtitle>Biophys J</addtitle><description>Striated muscle contraction is regulated by the actin binding proteins tropomyosin and troponin. Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated actin containing Δ14 TnT was more readily activated than wild-type regulated actin. We suggested that the equilibria among the inactive (blocked), intermediate (closed or calcium), and active (open or myosin) states was shifted to the active state. We now show that, in addition, such regulated actin filaments cannot enter the inactive or blocked state. Regulated actin containing Δ14 TnT had ATPase activities in the absence of Ca2+ that were higher than wild-type filaments but far below the fully active rate. The rapid dissociation of S1-ATP from regulated actin filaments containing Δ14 TnT and acrylodan-labeled tropomyosin did not show the fluorescence increase characteristic of moving to the inactive state. Replacing wild-type TnI with S45E TnI, that favors the inactive state, did not restore the fluorescence change. We conclude that TnT has a previously unrecognized role in forming the inactive state of regulated actin.</description><subject>2-Naphthylamine - analogs & derivatives</subject><subject>2-Naphthylamine - metabolism</subject><subject>actin</subject><subject>Actins - metabolism</subject><subject>Adenosine triphosphatase</subject><subject>Adenosine Triphosphate - metabolism</subject><subject>adenosinetriphosphatase</subject><subject>Animals</subject><subject>Calcium</subject><subject>Calcium - pharmacology</subject><subject>cardiomyopathy</subject><subject>dissociation</subject><subject>Ethylmaleimide - pharmacology</subject><subject>Fluorescence</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Light</subject><subject>microfilaments</subject><subject>Models, Biological</subject><subject>muscle contraction</subject><subject>Muscle, Motility, and Motor Proteins</subject><subject>Muscle, Skeletal - enzymology</subject><subject>muscular diseases</subject><subject>Mutant Proteins - metabolism</subject><subject>myosin</subject><subject>Myosins - metabolism</subject><subject>Proteins</subject><subject>Scattering, Radiation</subject><subject>striated muscle</subject><subject>Structure-Activity Relationship</subject><subject>Time Factors</subject><subject>Tropomyosin - metabolism</subject><subject>tropomyosins</subject><subject>troponin T</subject><subject>Troponin T - chemistry</subject><subject>Troponin T - metabolism</subject><issn>0006-3495</issn><issn>1542-0086</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV-L1DAUxYMo7rj6AXzRwD633vxrWgRhGVYdWBHc7nNI03Q2ZSYZk3TAb2-GWRd98SEkcH_n3EMOQm8J1ARI82Guh8NcUyC0Bl4Dk8_QighOK4C2eY5WANBUjHfiAr1KaYYCCiAv0QWlkjDRdCuk-geL11Vv4975JeEw4T6GQ_DO4x5vEr5Jyfrs9A5PIeJv2vlcjvNbnIty47XJ7mjxXdbZntQ_7HbZlfeIr8vEv0YvJr1L9s3jfYnuP9_066_V7fcvm_X1bWUEsFxJyUwrKBm5YN04tZRwM0quu4G2RFpBJ2hsB60cTEuZGEWrQVNqR0vBGD6wS_Tp7HtYhr0dTckc9U4dotvr-EsF7dS_E-8e1DYcFWNNS7gsBlePBjH8XGzKag5L9CWzIkCBUUklFIqcKRNDStFOTxsIqFMnalalE3XqRAFXpZOiefd3tCfFnxIK8P4MTDoovY0uqfu74iBKYYTyjhTi45mw5QuPzkaVjLPe2NFFa7Iag_tPgN9dMaVM</recordid><startdate>20120606</startdate><enddate>20120606</enddate><creator>Franklin, Andrew J.</creator><creator>Baxley, Tamatha</creator><creator>Kobayashi, Tomoyoshi</creator><creator>Chalovich, Joseph M.</creator><general>Elsevier Inc</general><general>Biophysical Society</general><general>The Biophysical Society</general><scope>6I.</scope><scope>AAFTH</scope><scope>FBQ</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7QP</scope><scope>7TK</scope><scope>7TM</scope><scope>7U9</scope><scope>8FD</scope><scope>FR3</scope><scope>H94</scope><scope>K9.</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20120606</creationdate><title>The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin</title><author>Franklin, Andrew J. ; Baxley, Tamatha ; Kobayashi, Tomoyoshi ; Chalovich, Joseph M.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c503t-773c8521d4539df8214cd74a9b2817e52f06e9087bc8235d58a0a22ede20cc4b3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>2-Naphthylamine - analogs & derivatives</topic><topic>2-Naphthylamine - metabolism</topic><topic>actin</topic><topic>Actins - metabolism</topic><topic>Adenosine triphosphatase</topic><topic>Adenosine Triphosphate - metabolism</topic><topic>adenosinetriphosphatase</topic><topic>Animals</topic><topic>Calcium</topic><topic>Calcium - pharmacology</topic><topic>cardiomyopathy</topic><topic>dissociation</topic><topic>Ethylmaleimide - pharmacology</topic><topic>Fluorescence</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Light</topic><topic>microfilaments</topic><topic>Models, Biological</topic><topic>muscle contraction</topic><topic>Muscle, Motility, and Motor Proteins</topic><topic>Muscle, Skeletal - enzymology</topic><topic>muscular diseases</topic><topic>Mutant Proteins - metabolism</topic><topic>myosin</topic><topic>Myosins - metabolism</topic><topic>Proteins</topic><topic>Scattering, Radiation</topic><topic>striated muscle</topic><topic>Structure-Activity Relationship</topic><topic>Time Factors</topic><topic>Tropomyosin - metabolism</topic><topic>tropomyosins</topic><topic>troponin T</topic><topic>Troponin T - chemistry</topic><topic>Troponin T - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Franklin, Andrew J.</creatorcontrib><creatorcontrib>Baxley, Tamatha</creatorcontrib><creatorcontrib>Kobayashi, Tomoyoshi</creatorcontrib><creatorcontrib>Chalovich, Joseph M.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>AGRIS</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biophysical journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Franklin, Andrew J.</au><au>Baxley, Tamatha</au><au>Kobayashi, Tomoyoshi</au><au>Chalovich, Joseph M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin</atitle><jtitle>Biophysical journal</jtitle><addtitle>Biophys J</addtitle><date>2012-06-06</date><risdate>2012</risdate><volume>102</volume><issue>11</issue><spage>2536</spage><epage>2544</epage><pages>2536-2544</pages><issn>0006-3495</issn><eissn>1542-0086</eissn><abstract>Striated muscle contraction is regulated by the actin binding proteins tropomyosin and troponin. Defects in these proteins lead to myopathies and cardiomyopathies. Deletion of the 14 C-terminal residues of cardiac troponin T leads to hypertrophic cardiomyopathy. We showed earlier that regulated actin containing Δ14 TnT was more readily activated than wild-type regulated actin. We suggested that the equilibria among the inactive (blocked), intermediate (closed or calcium), and active (open or myosin) states was shifted to the active state. We now show that, in addition, such regulated actin filaments cannot enter the inactive or blocked state. Regulated actin containing Δ14 TnT had ATPase activities in the absence of Ca2+ that were higher than wild-type filaments but far below the fully active rate. The rapid dissociation of S1-ATP from regulated actin filaments containing Δ14 TnT and acrylodan-labeled tropomyosin did not show the fluorescence increase characteristic of moving to the inactive state. Replacing wild-type TnI with S45E TnI, that favors the inactive state, did not restore the fluorescence change. We conclude that TnT has a previously unrecognized role in forming the inactive state of regulated actin.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22713569</pmid><doi>10.1016/j.bpj.2012.04.037</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Biophysical journal, 2012-06, Vol.102 (11), p.2536-2544 |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present); PubMed Central |
| subjects | 2-Naphthylamine - analogs & derivatives 2-Naphthylamine - metabolism actin Actins - metabolism Adenosine triphosphatase Adenosine Triphosphate - metabolism adenosinetriphosphatase Animals Calcium Calcium - pharmacology cardiomyopathy dissociation Ethylmaleimide - pharmacology Fluorescence Humans Kinetics Light microfilaments Models, Biological muscle contraction Muscle, Motility, and Motor Proteins Muscle, Skeletal - enzymology muscular diseases Mutant Proteins - metabolism myosin Myosins - metabolism Proteins Scattering, Radiation striated muscle Structure-Activity Relationship Time Factors Tropomyosin - metabolism tropomyosins troponin T Troponin T - chemistry Troponin T - metabolism |
| title | The C-Terminus of Troponin T Is Essential for Maintaining the Inactive State of Regulated Actin |
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