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The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a
The angiotensin II type 1 receptor-associated protein (Atrap) is highly expressed in the heart, but its function in the heart is unknown. We hypothesized that cardiac Atrap may interact with proteins other than the AT1 receptor. To identify potential novel interacting partners of Atrap, pull-down as...
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Published in: | Cardiovascular research 2016-06, Vol.110 (3), p.359-370 |
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creator | Mederle, Katharina Gess, Bernhard Pluteanu, Florentina Plackic, Jelena Tiefenbach, Klaus-Jürgen Grill, Alexandra Kockskämper, Jens Castrop, Hayo |
description | The angiotensin II type 1 receptor-associated protein (Atrap) is highly expressed in the heart, but its function in the heart is unknown. We hypothesized that cardiac Atrap may interact with proteins other than the AT1 receptor.
To identify potential novel interacting partners of Atrap, pull-down assays were performed. Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon resonance (SPR) spectroscopy. Atrap enhanced the SERCA-dependent Ca(2+) uptake in isolated SR membrane vesicles. Furthermore, sarcomere shortenings and [Ca(2+)]i transients (CaTs) were determined in ventricular myocytes isolated from Atrap-/- and wild-type (WT) mice. The amplitudes of CaTs and sarcomere shortenings were similar in Atrap-/- and WT myocytes. However, the CaT decay and sarcomere re-lengthening were prolonged in Atrap-/- myocytes. To further evaluate the functional relevance of the Atrap-SERCA2a interaction in vivo, left-ventricular function was assessed in WT and Atrap-/- mice. The heart rates (564 ± 10 b.p.m. vs. 560 ± 11 b.p.m.; P = 0.80) and ejection fractions (71.3 ± 1.3 vs. 72 ± 1.8%; P = 0.79) were similar in WT and Atrap-/- mice, respectively (n = 15 for each genotype). However, the maximum filling rate (dV/dtmax) was markedly decreased in Atrap-/- (725 ± 48 µL/s) compared with WT mice (1065 ± 122 µL/s; P = 0.01; n = 15).
We identified Atrap as a novel regulatory protein of the cardiac Ca(2+)-ATPase SERCA2a. We suggest that Atrap enhances the activity of SERCA2a and, consequently, facilitates ventricular relaxation. |
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To identify potential novel interacting partners of Atrap, pull-down assays were performed. Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon resonance (SPR) spectroscopy. Atrap enhanced the SERCA-dependent Ca(2+) uptake in isolated SR membrane vesicles. Furthermore, sarcomere shortenings and [Ca(2+)]i transients (CaTs) were determined in ventricular myocytes isolated from Atrap-/- and wild-type (WT) mice. The amplitudes of CaTs and sarcomere shortenings were similar in Atrap-/- and WT myocytes. However, the CaT decay and sarcomere re-lengthening were prolonged in Atrap-/- myocytes. To further evaluate the functional relevance of the Atrap-SERCA2a interaction in vivo, left-ventricular function was assessed in WT and Atrap-/- mice. The heart rates (564 ± 10 b.p.m. vs. 560 ± 11 b.p.m.; P = 0.80) and ejection fractions (71.3 ± 1.3 vs. 72 ± 1.8%; P = 0.79) were similar in WT and Atrap-/- mice, respectively (n = 15 for each genotype). However, the maximum filling rate (dV/dtmax) was markedly decreased in Atrap-/- (725 ± 48 µL/s) compared with WT mice (1065 ± 122 µL/s; P = 0.01; n = 15).
We identified Atrap as a novel regulatory protein of the cardiac Ca(2+)-ATPase SERCA2a. We suggest that Atrap enhances the activity of SERCA2a and, consequently, facilitates ventricular relaxation.</description><identifier>EISSN: 1755-3245</identifier><identifier>DOI: 10.1093/cvr/cvw064</identifier><identifier>PMID: 27015675</identifier><language>eng</language><publisher>England</publisher><subject>Adaptor Proteins, Signal Transducing - deficiency ; Adaptor Proteins, Signal Transducing - genetics ; Adaptor Proteins, Signal Transducing - metabolism ; Animals ; Calcium Signaling ; Diastole ; Enzyme Activation ; HEK293 Cells ; Homeodomain Proteins - metabolism ; Humans ; Immunoprecipitation ; Mice, 129 Strain ; Mice, Inbred C57BL ; Mice, Knockout ; Myocytes, Cardiac - enzymology ; Protein Binding ; Proteomics - methods ; Sarcomeres - enzymology ; Sarcoplasmic Reticulum - enzymology ; Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Surface Plasmon Resonance ; Transfection ; Ventricular Function, Left</subject><ispartof>Cardiovascular research, 2016-06, Vol.110 (3), p.359-370</ispartof><rights>Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2016. For permissions please email: journals.permissions@oup.com.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27015675$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mederle, Katharina</creatorcontrib><creatorcontrib>Gess, Bernhard</creatorcontrib><creatorcontrib>Pluteanu, Florentina</creatorcontrib><creatorcontrib>Plackic, Jelena</creatorcontrib><creatorcontrib>Tiefenbach, Klaus-Jürgen</creatorcontrib><creatorcontrib>Grill, Alexandra</creatorcontrib><creatorcontrib>Kockskämper, Jens</creatorcontrib><creatorcontrib>Castrop, Hayo</creatorcontrib><title>The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a</title><title>Cardiovascular research</title><addtitle>Cardiovasc Res</addtitle><description>The angiotensin II type 1 receptor-associated protein (Atrap) is highly expressed in the heart, but its function in the heart is unknown. We hypothesized that cardiac Atrap may interact with proteins other than the AT1 receptor.
To identify potential novel interacting partners of Atrap, pull-down assays were performed. Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon resonance (SPR) spectroscopy. Atrap enhanced the SERCA-dependent Ca(2+) uptake in isolated SR membrane vesicles. Furthermore, sarcomere shortenings and [Ca(2+)]i transients (CaTs) were determined in ventricular myocytes isolated from Atrap-/- and wild-type (WT) mice. The amplitudes of CaTs and sarcomere shortenings were similar in Atrap-/- and WT myocytes. However, the CaT decay and sarcomere re-lengthening were prolonged in Atrap-/- myocytes. To further evaluate the functional relevance of the Atrap-SERCA2a interaction in vivo, left-ventricular function was assessed in WT and Atrap-/- mice. The heart rates (564 ± 10 b.p.m. vs. 560 ± 11 b.p.m.; P = 0.80) and ejection fractions (71.3 ± 1.3 vs. 72 ± 1.8%; P = 0.79) were similar in WT and Atrap-/- mice, respectively (n = 15 for each genotype). However, the maximum filling rate (dV/dtmax) was markedly decreased in Atrap-/- (725 ± 48 µL/s) compared with WT mice (1065 ± 122 µL/s; P = 0.01; n = 15).
We identified Atrap as a novel regulatory protein of the cardiac Ca(2+)-ATPase SERCA2a. We suggest that Atrap enhances the activity of SERCA2a and, consequently, facilitates ventricular relaxation.</description><subject>Adaptor Proteins, Signal Transducing - deficiency</subject><subject>Adaptor Proteins, Signal Transducing - genetics</subject><subject>Adaptor Proteins, Signal Transducing - metabolism</subject><subject>Animals</subject><subject>Calcium Signaling</subject><subject>Diastole</subject><subject>Enzyme Activation</subject><subject>HEK293 Cells</subject><subject>Homeodomain Proteins - metabolism</subject><subject>Humans</subject><subject>Immunoprecipitation</subject><subject>Mice, 129 Strain</subject><subject>Mice, Inbred C57BL</subject><subject>Mice, Knockout</subject><subject>Myocytes, Cardiac - enzymology</subject><subject>Protein Binding</subject><subject>Proteomics - methods</subject><subject>Sarcomeres - enzymology</subject><subject>Sarcoplasmic Reticulum - enzymology</subject><subject>Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism</subject><subject>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</subject><subject>Surface Plasmon Resonance</subject><subject>Transfection</subject><subject>Ventricular Function, Left</subject><issn>1755-3245</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><recordid>eNo1kE1LxDAYhIMg7rp68QdIjoJUkzZv0x5LWT9gQdH1XN5t32qWfpmkiv_egOthmMM8DMMwdiHFjRR5clt_2aBvkaojtpQaIEpiBQt26txeCAGg1QlbxFpISDUsWbP9II7Duxk9Dc4M3FJNkx9thM6NtUFPDZ9sSENWeIsTN44jd970c4cB5GPLfSip0TYGa15ifB0V22d0xF_XL2UR4xk7brFzdH7wFXu7W2_Lh2jzdP9YFptoH6vER0po2jUtZE2bykTmUoFO46wBCUB5DYSUoop3kEkgkSlQgYtRKY3YSknJil399YbBnzM5X_XG1dR1ONA4u0rqXKg0y8JRK3Z5QOddT001WdOj_an-n0l-AetDYiI</recordid><startdate>20160601</startdate><enddate>20160601</enddate><creator>Mederle, Katharina</creator><creator>Gess, Bernhard</creator><creator>Pluteanu, Florentina</creator><creator>Plackic, Jelena</creator><creator>Tiefenbach, Klaus-Jürgen</creator><creator>Grill, Alexandra</creator><creator>Kockskämper, Jens</creator><creator>Castrop, Hayo</creator><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>7X8</scope></search><sort><creationdate>20160601</creationdate><title>The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a</title><author>Mederle, Katharina ; Gess, Bernhard ; Pluteanu, Florentina ; Plackic, Jelena ; Tiefenbach, Klaus-Jürgen ; Grill, Alexandra ; Kockskämper, Jens ; Castrop, Hayo</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-j243t-407ebdf58df613191457628d5155e9c5eae6a42b5815e08454f612a447aaf11e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Adaptor Proteins, Signal Transducing - deficiency</topic><topic>Adaptor Proteins, Signal Transducing - genetics</topic><topic>Adaptor Proteins, Signal Transducing - metabolism</topic><topic>Animals</topic><topic>Calcium Signaling</topic><topic>Diastole</topic><topic>Enzyme Activation</topic><topic>HEK293 Cells</topic><topic>Homeodomain Proteins - metabolism</topic><topic>Humans</topic><topic>Immunoprecipitation</topic><topic>Mice, 129 Strain</topic><topic>Mice, Inbred C57BL</topic><topic>Mice, Knockout</topic><topic>Myocytes, Cardiac - enzymology</topic><topic>Protein Binding</topic><topic>Proteomics - methods</topic><topic>Sarcomeres - enzymology</topic><topic>Sarcoplasmic Reticulum - enzymology</topic><topic>Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism</topic><topic>Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization</topic><topic>Surface Plasmon Resonance</topic><topic>Transfection</topic><topic>Ventricular Function, Left</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mederle, Katharina</creatorcontrib><creatorcontrib>Gess, Bernhard</creatorcontrib><creatorcontrib>Pluteanu, Florentina</creatorcontrib><creatorcontrib>Plackic, Jelena</creatorcontrib><creatorcontrib>Tiefenbach, Klaus-Jürgen</creatorcontrib><creatorcontrib>Grill, Alexandra</creatorcontrib><creatorcontrib>Kockskämper, Jens</creatorcontrib><creatorcontrib>Castrop, Hayo</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>MEDLINE - Academic</collection><jtitle>Cardiovascular research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mederle, Katharina</au><au>Gess, Bernhard</au><au>Pluteanu, Florentina</au><au>Plackic, Jelena</au><au>Tiefenbach, Klaus-Jürgen</au><au>Grill, Alexandra</au><au>Kockskämper, Jens</au><au>Castrop, Hayo</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a</atitle><jtitle>Cardiovascular research</jtitle><addtitle>Cardiovasc Res</addtitle><date>2016-06-01</date><risdate>2016</risdate><volume>110</volume><issue>3</issue><spage>359</spage><epage>370</epage><pages>359-370</pages><eissn>1755-3245</eissn><abstract>The angiotensin II type 1 receptor-associated protein (Atrap) is highly expressed in the heart, but its function in the heart is unknown. We hypothesized that cardiac Atrap may interact with proteins other than the AT1 receptor.
To identify potential novel interacting partners of Atrap, pull-down assays were performed. Sequencing by MALDI-MS of the isolated complexes showed that Atrap interacts with the cardiac Ca(2+)-ATPase SERCA2a. The interaction between Atrap and SERCA2a was confirmed by co-immunoprecipitation and by surface plasmon resonance (SPR) spectroscopy. Atrap enhanced the SERCA-dependent Ca(2+) uptake in isolated SR membrane vesicles. Furthermore, sarcomere shortenings and [Ca(2+)]i transients (CaTs) were determined in ventricular myocytes isolated from Atrap-/- and wild-type (WT) mice. The amplitudes of CaTs and sarcomere shortenings were similar in Atrap-/- and WT myocytes. However, the CaT decay and sarcomere re-lengthening were prolonged in Atrap-/- myocytes. To further evaluate the functional relevance of the Atrap-SERCA2a interaction in vivo, left-ventricular function was assessed in WT and Atrap-/- mice. The heart rates (564 ± 10 b.p.m. vs. 560 ± 11 b.p.m.; P = 0.80) and ejection fractions (71.3 ± 1.3 vs. 72 ± 1.8%; P = 0.79) were similar in WT and Atrap-/- mice, respectively (n = 15 for each genotype). However, the maximum filling rate (dV/dtmax) was markedly decreased in Atrap-/- (725 ± 48 µL/s) compared with WT mice (1065 ± 122 µL/s; P = 0.01; n = 15).
We identified Atrap as a novel regulatory protein of the cardiac Ca(2+)-ATPase SERCA2a. We suggest that Atrap enhances the activity of SERCA2a and, consequently, facilitates ventricular relaxation.</abstract><cop>England</cop><pmid>27015675</pmid><doi>10.1093/cvr/cvw064</doi><tpages>12</tpages><oa>free_for_read</oa></addata></record> |
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subjects | Adaptor Proteins, Signal Transducing - deficiency Adaptor Proteins, Signal Transducing - genetics Adaptor Proteins, Signal Transducing - metabolism Animals Calcium Signaling Diastole Enzyme Activation HEK293 Cells Homeodomain Proteins - metabolism Humans Immunoprecipitation Mice, 129 Strain Mice, Inbred C57BL Mice, Knockout Myocytes, Cardiac - enzymology Protein Binding Proteomics - methods Sarcomeres - enzymology Sarcoplasmic Reticulum - enzymology Sarcoplasmic Reticulum Calcium-Transporting ATPases - metabolism Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization Surface Plasmon Resonance Transfection Ventricular Function, Left |
title | The angiotensin receptor-associated protein Atrap is a stimulator of the cardiac Ca2+-ATPase SERCA2a |
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