Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling
Abstract The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2 -adrenergic receptor (β2 AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster reso...
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| Veröffentlicht in: | Journal of molecular and cellular cardiology 2014-02, Vol.67, p.38-48 |
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| creator | Wright, Peter T Nikolaev, Viacheslav O O'Hara, Thomas Diakonov, Ivan Bhargava, Anamika Tokar, Sergiy Schobesberger, Sophie Shevchuk, Andrew I Sikkel, Markus B Wilkinson, Ross Trayanova, Natalia A Lyon, Alexander R Harding, Sian E Gorelik, Julia |
| description | Abstract The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2 -adrenergic receptor (β2 AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2 AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2 AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2 AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2 AR response could only be generated in T-tubules. However, the normally compartmentalized β2 AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2 AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2 AR and compartmentation of β2 AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors. |
| doi_str_mv | 10.1016/j.yjmcc.2013.12.003 |
| format | Article |
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We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2 AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2 AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2 AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2 AR response could only be generated in T-tubules. However, the normally compartmentalized β2 AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2 AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2 AR and compartmentation of β2 AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors.</description><identifier>ISSN: 0022-2828</identifier><identifier>EISSN: 1095-8584</identifier><identifier>DOI: 10.1016/j.yjmcc.2013.12.003</identifier><identifier>PMID: 24345421</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Animals ; Beta-adrenergic receptors ; Blotting, Western ; Cardiomyocytes ; Cardiovascular ; Caveolin 3 - genetics ; Caveolin 3 - metabolism ; Compartment Syndromes - physiopathology ; Computer Simulation ; Cyclic AMP - metabolism ; FRET ; Gene Expression ; Heart Failure - physiopathology ; Myocytes, Cardiac - metabolism ; Rats ; Receptors, Adrenergic, beta-2 - metabolism ; SICM ; Signal Transduction ; T-tubules</subject><ispartof>Journal of molecular and cellular cardiology, 2014-02, Vol.67, p.38-48</ispartof><rights>The Authors</rights><rights>2013 The Authors</rights><rights>Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.</rights><rights>2014 Elsevier Ltd. All rights reserved. 2014</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c514t-ab900a21bdbd40c9806d4ba824226d25336895c84bd656a3c3a21c88708ae2713</citedby><cites>FETCH-LOGICAL-c514t-ab900a21bdbd40c9806d4ba824226d25336895c84bd656a3c3a21c88708ae2713</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.yjmcc.2013.12.003$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3548,27922,27923,45993</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24345421$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wright, Peter T</creatorcontrib><creatorcontrib>Nikolaev, Viacheslav O</creatorcontrib><creatorcontrib>O'Hara, Thomas</creatorcontrib><creatorcontrib>Diakonov, Ivan</creatorcontrib><creatorcontrib>Bhargava, Anamika</creatorcontrib><creatorcontrib>Tokar, Sergiy</creatorcontrib><creatorcontrib>Schobesberger, Sophie</creatorcontrib><creatorcontrib>Shevchuk, Andrew I</creatorcontrib><creatorcontrib>Sikkel, Markus B</creatorcontrib><creatorcontrib>Wilkinson, Ross</creatorcontrib><creatorcontrib>Trayanova, Natalia A</creatorcontrib><creatorcontrib>Lyon, Alexander R</creatorcontrib><creatorcontrib>Harding, Sian E</creatorcontrib><creatorcontrib>Gorelik, Julia</creatorcontrib><title>Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling</title><title>Journal of molecular and cellular cardiology</title><addtitle>J Mol Cell Cardiol</addtitle><description>Abstract The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2 -adrenergic receptor (β2 AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2 AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2 AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2 AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2 AR response could only be generated in T-tubules. However, the normally compartmentalized β2 AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2 AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2 AR and compartmentation of β2 AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors.</description><subject>Animals</subject><subject>Beta-adrenergic receptors</subject><subject>Blotting, Western</subject><subject>Cardiomyocytes</subject><subject>Cardiovascular</subject><subject>Caveolin 3 - genetics</subject><subject>Caveolin 3 - metabolism</subject><subject>Compartment Syndromes - physiopathology</subject><subject>Computer Simulation</subject><subject>Cyclic AMP - metabolism</subject><subject>FRET</subject><subject>Gene Expression</subject><subject>Heart Failure - physiopathology</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Rats</subject><subject>Receptors, Adrenergic, beta-2 - metabolism</subject><subject>SICM</subject><subject>Signal Transduction</subject><subject>T-tubules</subject><issn>0022-2828</issn><issn>1095-8584</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkktv1DAUhS0EokPhFyChLNkk-JnaCypVI6CVikAC1pZj30kdkniwnZHy7_EwpQI2rLzwOec-vovQS4Ibgkn7ZmjWYbK2oZiwhtAGY_YIbQhWopZC8sdogzGlNZVUnqFnKQ0YY8UZe4rOKGdccEo26G5rDhBGP9esitAvo8mQKhumvYl5gjmb7MNchV1lTXQ-TGuwa4aqg2xobVyEGWLvbTFb2OcQ6wmcLyGuslcfP1fJ97Mp8f1z9GRnxgQv7t9z9O39u6_b6_r204eb7dVtbQXhuTadwthQ0rnOcWyVxK3jnZGUU9o6KhhrpRJW8s61ojXMsiK2Ul5gaYBeEHaOLk-5-6UrrdgyQjSj3kc_mbjqYLz--2f2d7oPB81p2yqGS8Dr-4AYfiyQsp58sjCOZoawJE24oq1SQokiZSepjSGlCLuHMgTrIyM96F-M9JGRJlQXRsX16s8OHzy_oRTB25MAyp4OHqJO1sNsy2LLlrN2wf-nwOU_flsIeGvG77BCGsISC5MyiU7FoL8cz-R4JYQVt6CY_QTfm7qL</recordid><startdate>20140201</startdate><enddate>20140201</enddate><creator>Wright, Peter T</creator><creator>Nikolaev, Viacheslav O</creator><creator>O'Hara, Thomas</creator><creator>Diakonov, Ivan</creator><creator>Bhargava, Anamika</creator><creator>Tokar, Sergiy</creator><creator>Schobesberger, Sophie</creator><creator>Shevchuk, Andrew I</creator><creator>Sikkel, Markus B</creator><creator>Wilkinson, Ross</creator><creator>Trayanova, Natalia A</creator><creator>Lyon, Alexander R</creator><creator>Harding, Sian E</creator><creator>Gorelik, Julia</creator><general>Elsevier Ltd</general><scope>6I.</scope><scope>AAFTH</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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140201</creationdate><title>Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling</title><author>Wright, Peter T ; Nikolaev, Viacheslav O ; O'Hara, Thomas ; Diakonov, Ivan ; Bhargava, Anamika ; Tokar, Sergiy ; Schobesberger, Sophie ; Shevchuk, Andrew I ; Sikkel, Markus B ; Wilkinson, Ross ; Trayanova, Natalia A ; Lyon, Alexander R ; Harding, Sian E ; Gorelik, Julia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c514t-ab900a21bdbd40c9806d4ba824226d25336895c84bd656a3c3a21c88708ae2713</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Animals</topic><topic>Beta-adrenergic receptors</topic><topic>Blotting, Western</topic><topic>Cardiomyocytes</topic><topic>Cardiovascular</topic><topic>Caveolin 3 - genetics</topic><topic>Caveolin 3 - metabolism</topic><topic>Compartment Syndromes - physiopathology</topic><topic>Computer Simulation</topic><topic>Cyclic AMP - metabolism</topic><topic>FRET</topic><topic>Gene Expression</topic><topic>Heart Failure - physiopathology</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Rats</topic><topic>Receptors, Adrenergic, beta-2 - metabolism</topic><topic>SICM</topic><topic>Signal Transduction</topic><topic>T-tubules</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wright, Peter T</creatorcontrib><creatorcontrib>Nikolaev, Viacheslav O</creatorcontrib><creatorcontrib>O'Hara, Thomas</creatorcontrib><creatorcontrib>Diakonov, Ivan</creatorcontrib><creatorcontrib>Bhargava, Anamika</creatorcontrib><creatorcontrib>Tokar, Sergiy</creatorcontrib><creatorcontrib>Schobesberger, Sophie</creatorcontrib><creatorcontrib>Shevchuk, Andrew I</creatorcontrib><creatorcontrib>Sikkel, Markus B</creatorcontrib><creatorcontrib>Wilkinson, Ross</creatorcontrib><creatorcontrib>Trayanova, Natalia A</creatorcontrib><creatorcontrib>Lyon, Alexander R</creatorcontrib><creatorcontrib>Harding, Sian E</creatorcontrib><creatorcontrib>Gorelik, Julia</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of molecular and cellular cardiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wright, Peter T</au><au>Nikolaev, Viacheslav O</au><au>O'Hara, Thomas</au><au>Diakonov, Ivan</au><au>Bhargava, Anamika</au><au>Tokar, Sergiy</au><au>Schobesberger, Sophie</au><au>Shevchuk, Andrew I</au><au>Sikkel, Markus B</au><au>Wilkinson, Ross</au><au>Trayanova, Natalia A</au><au>Lyon, Alexander R</au><au>Harding, Sian E</au><au>Gorelik, Julia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling</atitle><jtitle>Journal of molecular and cellular cardiology</jtitle><addtitle>J Mol Cell Cardiol</addtitle><date>2014-02-01</date><risdate>2014</risdate><volume>67</volume><spage>38</spage><epage>48</epage><pages>38-48</pages><issn>0022-2828</issn><eissn>1095-8584</eissn><abstract>Abstract The purpose of this study was to investigate whether caveolin-3 (Cav3) regulates localization of β2 -adrenergic receptor (β2 AR) and its cAMP signaling in healthy or failing cardiomyocytes. We co-expressed wildtype Cav3 or its dominant-negative mutant (Cav3DN) together with the Förster resonance energy transfer (FRET)-based cAMP sensor Epac2-camps in adult rat ventricular myocytes (ARVMs). FRET and scanning ion conductance microscopy were used to locally stimulate β2 AR and to measure cytosolic cAMP. Cav3 overexpression increased the number of caveolae and decreased the magnitude of β2 AR-cAMP signal. Conversely, Cav3DN expression resulted in an increased β2 AR-cAMP response without altering the whole-cell L-type calcium current. Following local stimulation of Cav3DN-expressing ARVMs, β2 AR response could only be generated in T-tubules. However, the normally compartmentalized β2 AR-cAMP signal became diffuse, similar to the situation observed in heart failure. Finally, overexpression of Cav3 in failing myocytes led to partial β2 AR redistribution back into the T-tubules. In conclusion, Cav3 plays a crucial role for the localization of β2 AR and compartmentation of β2 AR-cAMP signaling to the T-tubules of healthy ARVMs, and overexpression of Cav3 in failing myocytes can partially restore the disrupted localization of these receptors.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>24345421</pmid><doi>10.1016/j.yjmcc.2013.12.003</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Beta-adrenergic receptors Blotting, Western Cardiomyocytes Cardiovascular Caveolin 3 - genetics Caveolin 3 - metabolism Compartment Syndromes - physiopathology Computer Simulation Cyclic AMP - metabolism FRET Gene Expression Heart Failure - physiopathology Myocytes, Cardiac - metabolism Rats Receptors, Adrenergic, beta-2 - metabolism SICM Signal Transduction T-tubules |
| title | Caveolin-3 regulates compartmentation of cardiomyocyte beta2-adrenergic receptor-mediated cAMP signaling |
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