High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart
Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress....
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| Veröffentlicht in: | Scientific reports 2017-01, Vol.7 (1), p.40620-40620, Article 40620 |
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| creator | Aston, Daniel Capel, Rebecca A. Ford, Kerrie L. Christian, Helen C. Mirams, Gary R. Rog-Zielinska, Eva A. Kohl, Peter Galione, Antony Burton, Rebecca A. B. Terrar, Derek A. |
| description | Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart. |
| doi_str_mv | 10.1038/srep40620 |
| format | Article |
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B. ; Terrar, Derek A.</creator><creatorcontrib>Aston, Daniel ; Capel, Rebecca A. ; Ford, Kerrie L. ; Christian, Helen C. ; Mirams, Gary R. ; Rog-Zielinska, Eva A. ; Kohl, Peter ; Galione, Antony ; Burton, Rebecca A. B. ; Terrar, Derek A.</creatorcontrib><description>Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep40620</identifier><identifier>PMID: 28094777</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>13/51 ; 631/535/1258 ; 692/4019/592 ; Adenine ; Animals ; Biomarkers ; Calcium ; Calcium - metabolism ; Calcium Channels - metabolism ; Calcium phosphates ; Calcium Signaling ; Calcium signalling ; Cardiac muscle ; Cardiomyocytes ; Cell death ; Electron microscopy ; Fourier analysis ; Heart ; Heart diseases ; Heart Ventricles - cytology ; Heart Ventricles - metabolism ; Humanities and Social Sciences ; Hypotheses ; Kinases ; Lysosomal-Associated Membrane Protein 2 - metabolism ; Lysosomes ; Lysosomes - metabolism ; Lysosomes - ultrastructure ; Male ; Membranes ; Microscopy ; Mitochondria ; multidisciplinary ; Myocytes ; Myocytes, Cardiac - metabolism ; Myocytes, Cardiac - ultrastructure ; NAADP ; NADP - analogs & derivatives ; NADP - metabolism ; Nicotinic acid ; Organelles ; Organelles - metabolism ; Pharmacology ; Phosphorylation ; Physiology ; Proteins ; Pulmonary arteries ; Rabbits ; Reperfusion ; Sarcoplasmic reticulum ; Sarcoplasmic Reticulum - metabolism ; Sarcoplasmic Reticulum - ultrastructure ; Science ; Science (multidisciplinary) ; Ventricle</subject><ispartof>Scientific reports, 2017-01, Vol.7 (1), p.40620-40620, Article 40620</ispartof><rights>The Author(s) 2017</rights><rights>Copyright Nature Publishing Group Jan 2017</rights><rights>Copyright © 2017, The Author(s) 2017 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-79b6f94c1f11ccb04164cc4db23963f368262467a92205f7736222cf88c896ce3</citedby><cites>FETCH-LOGICAL-c438t-79b6f94c1f11ccb04164cc4db23963f368262467a92205f7736222cf88c896ce3</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/PMC5240626/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5240626/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,725,778,782,862,883,27907,27908,41103,42172,51559,53774,53776</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28094777$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Aston, Daniel</creatorcontrib><creatorcontrib>Capel, Rebecca A.</creatorcontrib><creatorcontrib>Ford, Kerrie L.</creatorcontrib><creatorcontrib>Christian, Helen C.</creatorcontrib><creatorcontrib>Mirams, Gary R.</creatorcontrib><creatorcontrib>Rog-Zielinska, Eva A.</creatorcontrib><creatorcontrib>Kohl, Peter</creatorcontrib><creatorcontrib>Galione, Antony</creatorcontrib><creatorcontrib>Burton, Rebecca A. B.</creatorcontrib><creatorcontrib>Terrar, Derek A.</creatorcontrib><title>High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart.</description><subject>13/51</subject><subject>631/535/1258</subject><subject>692/4019/592</subject><subject>Adenine</subject><subject>Animals</subject><subject>Biomarkers</subject><subject>Calcium</subject><subject>Calcium - metabolism</subject><subject>Calcium Channels - metabolism</subject><subject>Calcium phosphates</subject><subject>Calcium Signaling</subject><subject>Calcium signalling</subject><subject>Cardiac muscle</subject><subject>Cardiomyocytes</subject><subject>Cell death</subject><subject>Electron microscopy</subject><subject>Fourier analysis</subject><subject>Heart</subject><subject>Heart diseases</subject><subject>Heart Ventricles - cytology</subject><subject>Heart Ventricles - metabolism</subject><subject>Humanities and Social Sciences</subject><subject>Hypotheses</subject><subject>Kinases</subject><subject>Lysosomal-Associated Membrane Protein 2 - metabolism</subject><subject>Lysosomes</subject><subject>Lysosomes - metabolism</subject><subject>Lysosomes - ultrastructure</subject><subject>Male</subject><subject>Membranes</subject><subject>Microscopy</subject><subject>Mitochondria</subject><subject>multidisciplinary</subject><subject>Myocytes</subject><subject>Myocytes, Cardiac - metabolism</subject><subject>Myocytes, Cardiac - ultrastructure</subject><subject>NAADP</subject><subject>NADP - analogs & derivatives</subject><subject>NADP - metabolism</subject><subject>Nicotinic acid</subject><subject>Organelles</subject><subject>Organelles - metabolism</subject><subject>Pharmacology</subject><subject>Phosphorylation</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Pulmonary arteries</subject><subject>Rabbits</subject><subject>Reperfusion</subject><subject>Sarcoplasmic reticulum</subject><subject>Sarcoplasmic Reticulum - metabolism</subject><subject>Sarcoplasmic Reticulum - ultrastructure</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Ventricle</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkd9qFDEUxgdRbKm98AUk4E0rrObfJJMboRS1QkGweh2ymcxMykyy5iQtfQGf26xbl1Vzk5Dz4zvnfF_TvCT4LcGsewfJbTgWFD9pjinm7YoySp8evI-aU4BbXE9LFSfqeXNEO6y4lPK4-XnlxwklB3Eu2ceAIKdic0lmRu7O9y5Yh6CMo4MMKE8O3Zhk42Y2sHiLvrrsbZnLgoaYFkD1L8U-LsYHQPc-T-jC-r6CNznWJuhsfoAIcXFwjnz4rTc5k_KL5tlgZnCnj_dJ8_3jh2-XV6vrL58-X15cryxnXV5JtRaD4pYMhFi7xpwIbi3v15QpwQYmOiooF9IoSnE7SMkEpdQOXWc7JaxjJ837ne6mrBfXWxdy3VRvkl9MetDReP13JfhJj_FOt3TrsagCZ48CKf4o1RS9eLBunk1wsYAmnSBtKyRjFX39D3obSwp1vUop1WLF5FbwfEdV46BmOeyHIVhvA9b7gCv76nD6Pfknzgq82QFQS2F06aDlf2q_AL6gseU</recordid><startdate>20170117</startdate><enddate>20170117</enddate><creator>Aston, Daniel</creator><creator>Capel, Rebecca A.</creator><creator>Ford, Kerrie L.</creator><creator>Christian, Helen C.</creator><creator>Mirams, Gary R.</creator><creator>Rog-Zielinska, Eva A.</creator><creator>Kohl, Peter</creator><creator>Galione, Antony</creator><creator>Burton, Rebecca A. 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B. ; Terrar, Derek A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-79b6f94c1f11ccb04164cc4db23963f368262467a92205f7736222cf88c896ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>13/51</topic><topic>631/535/1258</topic><topic>692/4019/592</topic><topic>Adenine</topic><topic>Animals</topic><topic>Biomarkers</topic><topic>Calcium</topic><topic>Calcium - metabolism</topic><topic>Calcium Channels - metabolism</topic><topic>Calcium phosphates</topic><topic>Calcium Signaling</topic><topic>Calcium signalling</topic><topic>Cardiac muscle</topic><topic>Cardiomyocytes</topic><topic>Cell death</topic><topic>Electron microscopy</topic><topic>Fourier analysis</topic><topic>Heart</topic><topic>Heart diseases</topic><topic>Heart Ventricles - cytology</topic><topic>Heart Ventricles - metabolism</topic><topic>Humanities and Social Sciences</topic><topic>Hypotheses</topic><topic>Kinases</topic><topic>Lysosomal-Associated Membrane Protein 2 - metabolism</topic><topic>Lysosomes</topic><topic>Lysosomes - metabolism</topic><topic>Lysosomes - ultrastructure</topic><topic>Male</topic><topic>Membranes</topic><topic>Microscopy</topic><topic>Mitochondria</topic><topic>multidisciplinary</topic><topic>Myocytes</topic><topic>Myocytes, Cardiac - metabolism</topic><topic>Myocytes, Cardiac - ultrastructure</topic><topic>NAADP</topic><topic>NADP - analogs & derivatives</topic><topic>NADP - metabolism</topic><topic>Nicotinic acid</topic><topic>Organelles</topic><topic>Organelles - metabolism</topic><topic>Pharmacology</topic><topic>Phosphorylation</topic><topic>Physiology</topic><topic>Proteins</topic><topic>Pulmonary arteries</topic><topic>Rabbits</topic><topic>Reperfusion</topic><topic>Sarcoplasmic reticulum</topic><topic>Sarcoplasmic Reticulum - metabolism</topic><topic>Sarcoplasmic Reticulum - ultrastructure</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Ventricle</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Aston, Daniel</creatorcontrib><creatorcontrib>Capel, Rebecca A.</creatorcontrib><creatorcontrib>Ford, Kerrie L.</creatorcontrib><creatorcontrib>Christian, Helen C.</creatorcontrib><creatorcontrib>Mirams, Gary R.</creatorcontrib><creatorcontrib>Rog-Zielinska, Eva A.</creatorcontrib><creatorcontrib>Kohl, Peter</creatorcontrib><creatorcontrib>Galione, Antony</creatorcontrib><creatorcontrib>Burton, Rebecca A. B.</creatorcontrib><creatorcontrib>Terrar, Derek A.</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Aston, Daniel</au><au>Capel, Rebecca A.</au><au>Ford, Kerrie L.</au><au>Christian, Helen C.</au><au>Mirams, Gary R.</au><au>Rog-Zielinska, Eva A.</au><au>Kohl, Peter</au><au>Galione, Antony</au><au>Burton, Rebecca A. B.</au><au>Terrar, Derek A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2017-01-17</date><risdate>2017</risdate><volume>7</volume><issue>1</issue><spage>40620</spage><epage>40620</epage><pages>40620-40620</pages><artnum>40620</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Nicotinic Acid Adenine Dinucleotide Phosphate (NAADP) stimulates calcium release from acidic stores such as lysosomes and is a highly potent calcium-mobilising second messenger. NAADP plays an important role in calcium signalling in the heart under basal conditions and following β-adrenergic stress. Nevertheless, the spatial interaction of acidic stores with other parts of the calcium signalling apparatus in cardiac myocytes is unknown. We present evidence that lysosomes are intimately associated with the sarcoplasmic reticulum (SR) in ventricular myocytes; a median separation of 20 nm in 2D electron microscopy and 3.3 nm in 3D electron tomography indicates a genuine signalling microdomain between these organelles. Fourier analysis of immunolabelled lysosomes suggests a sarcomeric pattern (dominant wavelength 1.80 μm). Furthermore, we show that lysosomes form close associations with mitochondria (median separation 6.2 nm in 3D studies) which may provide a basis for the recently-discovered role of NAADP in reperfusion-induced cell death. The trigger hypothesis for NAADP action proposes that calcium release from acidic stores subsequently acts to enhance calcium release from the SR. This work provides structural evidence in cardiac myocytes to indicate the formation of microdomains between acidic and SR calcium stores, supporting emerging interpretations of NAADP physiology and pharmacology in heart.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>28094777</pmid><doi>10.1038/srep40620</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | 13/51 631/535/1258 692/4019/592 Adenine Animals Biomarkers Calcium Calcium - metabolism Calcium Channels - metabolism Calcium phosphates Calcium Signaling Calcium signalling Cardiac muscle Cardiomyocytes Cell death Electron microscopy Fourier analysis Heart Heart diseases Heart Ventricles - cytology Heart Ventricles - metabolism Humanities and Social Sciences Hypotheses Kinases Lysosomal-Associated Membrane Protein 2 - metabolism Lysosomes Lysosomes - metabolism Lysosomes - ultrastructure Male Membranes Microscopy Mitochondria multidisciplinary Myocytes Myocytes, Cardiac - metabolism Myocytes, Cardiac - ultrastructure NAADP NADP - analogs & derivatives NADP - metabolism Nicotinic acid Organelles Organelles - metabolism Pharmacology Phosphorylation Physiology Proteins Pulmonary arteries Rabbits Reperfusion Sarcoplasmic reticulum Sarcoplasmic Reticulum - metabolism Sarcoplasmic Reticulum - ultrastructure Science Science (multidisciplinary) Ventricle |
| title | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with Acidic Stores (lysosomes) in the heart |
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