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....
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
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Nature Publishing Group
2017
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| Online Access: | https://eprints.nottingham.ac.uk/42655/ |
| _version_ | 1848796538617200640 |
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| author | 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. |
| author_facet | 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. |
| author_sort | Aston, Daniel |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| 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. |
| first_indexed | 2025-11-14T19:49:35Z |
| format | Article |
| id | nottingham-42655 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:49:35Z |
| publishDate | 2017 |
| publisher | Nature Publishing Group |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-426552020-05-04T18:30:21Z https://eprints.nottingham.ac.uk/42655/ High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart 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. 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. Nature Publishing Group 2017-01-17 Article PeerReviewed 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. and Terrar, Derek A. (2017) High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart. Scientific Reports, 7 . 40620/1-40620/15. ISSN 2045-2322 https://www.nature.com/articles/srep40620 doi:10.1038/srep40620 doi:10.1038/srep40620 |
| spellingShingle | 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. High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title_full | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title_fullStr | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title_full_unstemmed | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title_short | High resolution structural evidence suggests the Sarcoplasmic Reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| title_sort | high resolution structural evidence suggests the sarcoplasmic reticulum forms microdomains with acidic stores (lysosomes) in the heart |
| url | https://eprints.nottingham.ac.uk/42655/ https://eprints.nottingham.ac.uk/42655/ https://eprints.nottingham.ac.uk/42655/ |