dc.creatorChrestia, Juan Facundo
dc.creatorBruzzone, Ariana
dc.creatorEsandi, María del Carmen
dc.creatorBouzat, Cecilia Beatriz
dc.date.accessioned2021-07-16T13:39:54Z
dc.date.accessioned2022-10-14T23:45:29Z
dc.date.available2021-07-16T13:39:54Z
dc.date.available2022-10-14T23:45:29Z
dc.date.created2021-07-16T13:39:54Z
dc.date.issued2021-05-24
dc.identifierChrestia, Juan Facundo; Bruzzone, Ariana; Esandi, María del Carmen; Bouzat, Cecilia Beatriz; Tyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor; Springer Nature Switzerland; Cellular and Molecular Life Sciences; 78; 24-5-2021; 5381–5395
dc.identifier1420-682X
dc.identifierhttp://hdl.handle.net/11336/136315
dc.identifier1420-9071
dc.identifierCONICET Digital
dc.identifierCONICET
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/4320949
dc.description.abstractThe α7 nicotinic acetylcholine receptor is involved in neurological, neurodegenerative, and inflammatory disorders. It operates both as a ligand-gated cationic channel and as a metabotropic receptor in neuronal and non-neuronal cells. As protein phosphorylation is an important cell function regulatory mechanism, deciphering how tyrosine phosphorylation modulates α7 dual ionotropic/metabotropic molecular function is required for understanding its integral role in physiological and pathological processes. α7 single-channel activity elicited by ACh appears as brief isolated openings and less often as episodes of few openings in quick succession. The reduction of phosphorylation by tyrosine kinase inhibition increases the duration and frequency of activation episodes, whereas the inhibition of phosphatases has the opposite effect. Removal of two tyrosine residues at the α7 intracellular domain recapitulates the effects mediated by tyrosine kinase inhibition. The tyrosine-free mutant receptor shows longer duration-activation episodes, reduced desensitization rate and significantly faster recovery from desensitization, indicating that phosphorylation decreases α7 channel activity by favoring the desensitized state. However, the mutant receptor is incapable of triggering ERK1/2 phosphorylation in response to the α7-agonist. Thus, while tyrosine phosphorylation is absolutely required for α7-triggered ERK pathway, it negatively modulates α7 ionotropic activity. Overall, phosphorylation/dephosphorylation events fine-tune the integrated cell response mediated by α7 activation, thus having a broad impact on α7 cholinergic signaling.
dc.languageeng
dc.publisherSpringer Nature Switzerland
dc.relationinfo:eu-repo/semantics/altIdentifier/url/https://link.springer.com/article/10.1007%2Fs00018-021-03853-3
dc.relationinfo:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.1007/s00018-021-03853-3
dc.rightshttps://creativecommons.org/licenses/by/2.5/ar/
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectCYS-LOOP RECEPTORS
dc.subjectDESENSITIZATION
dc.subjectPATCH-CLAMP
dc.subjectSINGLE-CHANNEL RECORDINGS
dc.subjectSRC-FAMILY KINASES
dc.titleTyrosine phosphorylation differentially fine-tunes ionotropic and metabotropic responses of human α7 nicotinic acetylcholine receptor
dc.typeinfo:eu-repo/semantics/article
dc.typeinfo:ar-repo/semantics/artículo
dc.typeinfo:eu-repo/semantics/publishedVersion


Este ítem pertenece a la siguiente institución