FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility
Compartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie,...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
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Springer Nature
2017
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| _version_ | 1797065201828233216 |
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| author | Surdo, N Berrera, M Koschinski, A Brescia, M Machado, M Carr, C Wright, P Gorelik, J Morotti, S Grandi, E Bers, D Pantano, S Zaccolo, M |
| author_facet | Surdo, N Berrera, M Koschinski, A Brescia, M Machado, M Carr, C Wright, P Gorelik, J Morotti, S Grandi, E Bers, D Pantano, S Zaccolo, M |
| author_sort | Surdo, N |
| collection | OXFORD |
| description | Compartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and myofilament sites, reveals differential kinetics and amplitudes of localized cAMP signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize cardiac contractility upon adrenergic activation. At low adrenergic levels, and those mimicking heart failure, differential local cAMP responses are exacerbated, with near abolition of cAMP signalling at certain locations. This work provides tools and fundamental mechanistic insights into subcellular adrenergic signalling in normal and pathological cardiac function. |
| first_indexed | 2024-03-06T21:25:16Z |
| format | Journal article |
| id | oxford-uuid:42e472d0-cfff-4024-963c-08a93bf7fcf5 |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:25:16Z |
| publishDate | 2017 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:42e472d0-cfff-4024-963c-08a93bf7fcf52022-03-26T14:52:02ZFRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractilityJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:42e472d0-cfff-4024-963c-08a93bf7fcf5Symplectic Elements at OxfordSpringer Nature2017Surdo, NBerrera, MKoschinski, ABrescia, MMachado, MCarr, CWright, PGorelik, JMorotti, SGrandi, EBers, DPantano, SZaccolo, MCompartmentalized cAMP/PKA signalling is now recognized as important for physiology and pathophysiology, yet a detailed understanding of the properties, regulation and function of local cAMP/PKA signals is lacking. Here we present a fluorescence resonance energy transfer (FRET)-based sensor, CUTie, which detects compartmentalized cAMP with unprecedented accuracy. CUTie, targeted to specific multiprotein complexes at discrete plasmalemmal, sarcoplasmic reticular and myofilament sites, reveals differential kinetics and amplitudes of localized cAMP signals. This nanoscopic heterogeneity of cAMP signals is necessary to optimize cardiac contractility upon adrenergic activation. At low adrenergic levels, and those mimicking heart failure, differential local cAMP responses are exacerbated, with near abolition of cAMP signalling at certain locations. This work provides tools and fundamental mechanistic insights into subcellular adrenergic signalling in normal and pathological cardiac function. |
| spellingShingle | Surdo, N Berrera, M Koschinski, A Brescia, M Machado, M Carr, C Wright, P Gorelik, J Morotti, S Grandi, E Bers, D Pantano, S Zaccolo, M FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title | FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title_full | FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title_fullStr | FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title_full_unstemmed | FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title_short | FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility |
| title_sort | fret biosensor uncovers camp nano domains at β adrenergic targets that dictate precise tuning of cardiac contractility |
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