{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T02:49:33Z","timestamp":1787626173189,"version":"build-2736575974"},"reference-count":53,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"11","license":[{"start":{"date-parts":[[2023,11,10]],"date-time":"2023-11-10T00:00:00Z","timestamp":1699574400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2023,11,10]]},"abstract":"<jats:sec>\n            <jats:title>Background:<\/jats:title>\n            <jats:p>\n              \u03b2\n              <jats:sub>1<\/jats:sub>\n              AR (beta-1 adrenergic receptor) and \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR (beta-2 adrenergic receptor)-mediated cyclic adenosine monophosphate signaling has distinct effects on cardiac function and heart failure progression. However, the mechanism regulating spatial localization and functional compartmentation of cardiac \u03b2-ARs remains elusive. Emerging evidence suggests that microtubule-dependent trafficking of mRNP (messenger ribonucleoprotein) and localized protein translation modulates protein compartmentation in cardiomyocytes. We hypothesized that \u03b2-AR compartmentation in cardiomyocytes is accomplished by selective trafficking of its mRNAs and localized translation.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>The localization pattern of \u03b2-AR mRNA was investigated using single molecule fluorescence in situ hybridization and subcellular nanobiopsy in rat cardiomyocytes. The role of microtubule on \u03b2-AR mRNA localization was studied using vinblastine, and its effect on receptor localization and function was evaluated with immunofluorescent and high-throughput F\u00f6rster resonance energy transfer microscopy. An mRNA protein co-detection assay identified plausible \u03b2-AR translation sites in cardiomyocytes. The mechanism by which \u03b2-AR mRNA is redistributed post\u2013heart failure was elucidated by single molecule fluorescence in situ hybridization, nanobiopsy, and high-throughput F\u00f6rster resonance energy transfer microscopy on 16 weeks post\u2013myocardial infarction and detubulated cardiomyocytes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>\n              \u03b2\n              <jats:sub>1<\/jats:sub>\n              AR and \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR mRNAs show differential localization in cardiomyocytes, with \u03b2\n              <jats:sub>1<\/jats:sub>\n              AR found in the perinuclear region and \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR showing diffuse distribution throughout the cell. Disruption of microtubules induces a shift of \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR transcripts toward the perinuclear region. The close proximity between \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR transcripts and translated proteins suggests that the translation process occurs in specialized, precisely defined cellular compartments. Redistribution of \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR transcripts is microtubule-dependent, as microtubule depolymerization markedly reduces the number of functional receptors on the membrane. In failing hearts, both \u03b2\n              <jats:sub>1<\/jats:sub>\n              AR and \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR mRNAs are redistributed toward the cell periphery, similar to what is seen in cardiomyocytes undergoing drug-induced detubulation. This suggests that t-tubule remodeling contributes to \u03b2-AR mRNA redistribution and impaired \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR function in failing hearts.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>\n              Asymmetrical microtubule-dependent trafficking dictates differential \u03b2\n              <jats:sub>1<\/jats:sub>\n              AR and \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR localization in healthy cardiomyocyte microtubules, underlying the distinctive compartmentation of the 2 \u03b2-ARs on the plasma membrane. The localization pattern is altered post\u2013myocardial infarction, resulting from transverse tubule remodeling, leading to distorted \u03b2\n              <jats:sub>2<\/jats:sub>\n              AR-mediated cyclic adenosine monophosphate signaling.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/circresaha.123.323174","type":"journal-article","created":{"date-parts":[[2023,10,23]],"date-time":"2023-10-23T09:00:20Z","timestamp":1698051620000},"page":"944-958","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":17,"title":["Microtubule-Mediated Regulation of \u03b2\n            <sub>2<\/sub>\n            AR Translation and Function in Failing Hearts"],"prefix":"10.1161","volume":"133","author":[{"given":"Zoe","family":"Kwan","sequence":"first","affiliation":[{"name":"National Heart and Lung Institute (Z.K., S.M., A.L., K.S.A., J.C., I.K., J.F., J.L.S.-A., C.A.M., P.S., B.W.-S., P.T.W., J.G.), Imperial College 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