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http://hdl.handle.net/2445/181261
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DC Field | Value | Language |
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dc.contributor.author | Ferrero, Jose J. | - |
dc.contributor.author | Alvarez, Ana M. | - |
dc.contributor.author | Ramírez-Franco, Jorge | - |
dc.contributor.author | Godino, María C. | - |
dc.contributor.author | Bartolomé-Martín, David | - |
dc.contributor.author | Aguado, Carolina | - |
dc.contributor.author | Torres, Magdalena | - |
dc.contributor.author | Luján, Rafael | - |
dc.contributor.author | Ciruela Alférez, Francisco | - |
dc.contributor.author | Sánchez-Prieto, José | - |
dc.date.accessioned | 2021-11-16T16:43:05Z | - |
dc.date.available | 2021-11-16T16:43:05Z | - |
dc.date.issued | 2013-10-25 | - |
dc.identifier.issn | 0021-9258 | - |
dc.identifier.uri | http://hdl.handle.net/2445/181261 | - |
dc.description.abstract | The adenylyl cyclase activator forskolin presynaptically facilitates synaptic transmission through cAMP-dependent protein kinase, PKA. However, cAMP also increases glutamate release via PKA-independent mechanisms, although the downstream presynaptic targets remain largely unknown. Here we found that a PKA-independent release component can be isolated in cerebrocortical nerve terminals after blocking Na+ channels with tetrodotoxin. 8-pCPT-2-O-Me-cAMP, 8pCPT, a specific activator of the exchange protein directly activated by cAMP, Epac, mimicks and occluded forskolin-induced release. The Epac mediated increase in release is dependent on phospholipase C, and increased phosphatidylinositol (4,5)-bisphosphate hydrolysis. Furthermore, the potentiation of release does not depend on protein kinase C, although it is reduced by the diacylglycerol-binding site antagonist calphostin C. Epac activation translocates the active zone protein Munc13-1 from soluble to particulate fractions, increases the association between Rab3A and Rim1αand redistributes synaptic vesicles to positions closer to the presynaptic membrane. We also found that the β-adrenergic receptor agonist, isoproterenol, mimicked all these responses consistent with high-resolution immunoelectron microscopy and immunocytochemical data showing presynaptic expression of the β-ARs at a subset of glutamatergic synapses of the cerebral cortex. It is concluded that β adrenergic receptors couple to a cAMP/Epac/PLC/Munc13/Rab3/Rim dependent pathway to enhance glutamate release at cerebrocortical nerve terminals. | - |
dc.format.extent | 16 p. | - |
dc.format.mimetype | application/pdf | - |
dc.language.iso | eng | - |
dc.publisher | American Society for Biochemistry and Molecular Biology | - |
dc.relation.isformatof | Reproducció del document publicat a: https://doi.org/10.1074/jbc.M113.463877 | - |
dc.relation.ispartof | Journal of Biological Chemistry, 2013, vol. 288, num. 43, p. 31370-31385 | - |
dc.relation.uri | https://doi.org/10.1074/jbc.M113.463877 | - |
dc.rights | (c) American Society for Biochemistry and Molecular Biology, 2013 | - |
dc.source | Articles publicats en revistes (Patologia i Terapèutica Experimental) | - |
dc.subject.classification | Receptors adrenèrgics | - |
dc.subject.classification | Nervis | - |
dc.subject.classification | Proteïnes | - |
dc.subject.other | Adrenaline receptors | - |
dc.subject.other | Nerves | - |
dc.subject.other | Proteins | - |
dc.title | β-Adrenergic receptors activate exchange protein directly activated by cAMP (Epac), translocate Munc13-1, and enhance the Rab3A-RIM1α interaction to potentiate glutamate release at cerebrocortical nerve terminal | - |
dc.type | info:eu-repo/semantics/article | - |
dc.type | info:eu-repo/semantics/publishedVersion | - |
dc.identifier.idgrec | 628803 | - |
dc.date.updated | 2021-11-16T16:43:06Z | - |
dc.rights.accessRights | info:eu-repo/semantics/openAccess | - |
dc.identifier.pmid | 24036110 | - |
Appears in Collections: | Articles publicats en revistes (Bioquímica i Biomedicina Molecular) Articles publicats en revistes (Patologia i Terapèutica Experimental) Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL)) |
Files in This Item:
File | Description | Size | Format | |
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628803.pdf | 3.82 MB | Adobe PDF | View/Open |
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