Mostrar el registro sencillo del ítem

dc.contributor.advisorPriori, Silvia G. 
dc.contributor.advisorCastillo Demetrio Julián, Santiago
dc.contributor.authorCancemi, Andrea
dc.date.accessioned2022-03-02T12:12:21Z
dc.date.available2022-03-02T12:12:21Z
dc.date.issued2021-11-19
dc.identifier.urihttp://hdl.handle.net/20.500.12105/13710
dc.description.abstractCalcium transients between the Sarcoplasmic Reticulum (SR) and the cytoplasm are essential for coordinated contraction in cardiomyocytes. Loss of the SR protein Calsequestrin 2 (CASQ2) causes the recessive form of Catecholaminergic Polymorphic Ventricular Tachycardia (CPVT2) by increasing the diastolic opening probability of the main SR calcium channel Ryanodine receptor 2 (RyR2), and by causing an unexplained decrease of its regulatory protein Triadin (TRDN). Here we studied the mechanisms of TRDN reduction in CASQ2-KO mice and show that ablation of CASQ2 activates histone-deacetylase HDAC6, which regulates several cellular processes. In CASQ2 deficient cardiomyocytes, HDAC6 reduces alpha-Tubulin acetylation, thus impairing microtubule stability and altering TRDN trafficking and co-localization with RyR2. Misplaced TRDN binds HSP70, forming Aggresomes that are degraded by autophagy. The study identifies a novel cascade of post-transcriptional events initiated by the loss of CASQ2 that leads to a major rearrangement of SR protein trafficking and stability in cardiomyocyteses_ES
dc.language.isoenges_ES
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/4.0/*
dc.subjectinherited arrhythmiases_ES
dc.subjectCpvTes_ES
dc.subjectMicrotubuluses_ES
dc.subjectautophagyes_ES
dc.titleCytoskeletal remodeling and enhanced autophagy drive an adaptive response to loss of Calsequestrin in a model of inherited arrhythmiases_ES
dc.typedoctoral thesises_ES
dc.rights.licenseAtribución-NoComercial-CompartirIgual 4.0 Internacional*
dc.identifier.doi10.4321/repisalud.13710
dc.description.peerreviewedNoes_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Cardiología Moleculares_ES
dc.repisalud.institucionCNICes_ES
dc.rights.accessRightsopen accesses_ES


Ficheros en el ítem

Acceso Abierto
Thumbnail

Este ítem aparece en la(s) siguiente(s) colección(ones)

Mostrar el registro sencillo del ítem

Atribución-NoComercial-CompartirIgual 4.0 Internacional
Este Item está sujeto a una licencia Creative Commons: Atribución-NoComercial-CompartirIgual 4.0 Internacional