The Golgi apparatus is a functionally distinct Ca2+ store regulated by PKA and Epac branches of the β1-adrenergic signaling pathway.
dc.contributor.author | Yang, Z. | * |
dc.contributor.author | Kirton, H.M. | * |
dc.contributor.author | MacDougall, D.A. | * |
dc.contributor.author | Boyle, J.P. | * |
dc.contributor.author | Deuchars, J. | * |
dc.contributor.author | Frater, B. | * |
dc.contributor.author | Ponnambalam, S. | * |
dc.contributor.author | Hardy, Matthew E. | * |
dc.contributor.author | White, M. | * |
dc.contributor.author | Calaghan, S.C. | * |
dc.contributor.author | Peers, C. | * |
dc.contributor.author | Steele, D.S. | * |
dc.date.accessioned | 2018-07-25T09:09:21Z | |
dc.date.available | 2018-07-25T09:09:21Z | |
dc.date.issued | 2015-10-13 | |
dc.identifier.citation | Yang Z, Kirton HM, MacDougall DA, Boyle JP, Deuchars J, Frater B, Ponnambalam S, Hardy ME, White E, Calaghan SC, Peers C and Steele DS (2015) The Golgi apparatus is a functionally distinct Ca2+ store regulated by the PKA and Epac branches of the β1-adrenergic signalling pathway. Science Signaling. 8 (398): ra101. | |
dc.identifier.uri | http://hdl.handle.net/10454/16503 | |
dc.description | Yes | |
dc.description.abstract | Ca2+ release from the Golgi apparatus regulates key functions of the organelle, including vesicle trafficking. However, the signaling pathways that control this form of Ca2+ release are poorly understood and evidence of discrete Golgi Ca2+ release events is lacking. Here, we identified the Golgi apparatus as the source of prolonged Ca2+ release events that originate from the nuclear ‘poles’ of primary cardiac cells. Once initiated, Golgi Ca2+ release was unaffected by global depletion of sarcoplasmic reticulum Ca2+, and disruption of the Golgi apparatus abolished Golgi Ca2+ release without affecting sarcoplasmic reticulum function, suggesting functional and anatomical independence of Golgi and sarcoplasmic reticulum Ca2+ stores. Maximal activation of β1-adrenoceptors had only a small stimulating effect on Golgi Ca2+ release. However, inhibition of phosphodiesterase (PDE) 3 or 4, or downregulation of PDE 3 and 4 in heart failure markedly potentiated β1-adrenergic stimulation of Golgi Ca2+ release, consistent with compartmentalization of cAMP signaling within the Golgi apparatus microenvironment. β1-adrenergic stimulation of Golgi Ca2+ release involved activation of both Epac and PKA signaling pathways and CaMKII. Interventions that stimulated Golgi Ca2+ release induced trafficking of vascular growth factor receptor-1 (VEGFR-1) from the Golgi apparatus to the surface membrane. These data establish the Golgi apparatus as a juxtanuclear focal point for Ca2+ and β1-adrenergic signaling, which functions independently from the sarcoplasmic reticulum and the global Ca2+ transients that underlie the primary contractile function of the cell. | |
dc.language.iso | en | |
dc.rights | © 2015 The Authors. Reproduced in accordance with the publisher's self-archiving policy. This is the author’s version of the work. It is posted here by permission of the AAAS for personal use, not for redistribution. The definitive version was published in Science Signaling in 2015. https://doi.org/10.1126/scisignal.aaa7677 | |
dc.subject | Golgi apparatus | |
dc.subject | Ca2+ store | |
dc.subject | PKA | |
dc.subject | Epac signaling pathway | |
dc.subject | β1-adrenergic signaling pathway | |
dc.subject | Signaling pathways | |
dc.title | The Golgi apparatus is a functionally distinct Ca2+ store regulated by PKA and Epac branches of the β1-adrenergic signaling pathway. | |
dc.status.refereed | Yes | |
dc.type.version | Accepted manuscript | |
dc.identifier.doi | https://doi.org/10.1126/scisignal.aaa7677 | |
dc.rights.license | Unspecified | |
refterms.dateFOA | 2018-07-25T09:09:24Z | |
dc.openaccess.status | openAccess |