Single-Molecule Imaging Reveals ERK-Dependent Spatial Translation in Cardiomyocytes.

Λεπτομέρειες βιβλιογραφικής εγγραφής
Τίτλος: Single-Molecule Imaging Reveals ERK-Dependent Spatial Translation in Cardiomyocytes.
Συγγραφείς: Erlich I; The Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Department of Physiology, Biophysics, and Systems Biology, Technion-Israel Institute of Technology, Haifa, Israel (I.E., G.D., R.H., I.K.)., Douvdevany G; The Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Department of Physiology, Biophysics, and Systems Biology, Technion-Israel Institute of Technology, Haifa, Israel (I.E., G.D., R.H., I.K.)., Haddad R; The Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Department of Physiology, Biophysics, and Systems Biology, Technion-Israel Institute of Technology, Haifa, Israel (I.E., G.D., R.H., I.K.)., Prosser BL; Department of Physiology, Pennsylvania Muscle Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia (B.L.P.)., Kehat I; The Rappaport Family Institute for Research in the Medical Sciences and the Ruth and Bruce Rappaport Faculty of Medicine, Department of Physiology, Biophysics, and Systems Biology, Technion-Israel Institute of Technology, Haifa, Israel (I.E., G.D., R.H., I.K.).
Πηγή: Circulation research [Circ Res] 2026 Sep 25; Vol. 139 (8), pp. e329033. Date of Electronic Publication: 2026 Aug 21.
Τύπος έκδοσης: Journal Article
Γλώσσα: English
Στοιχεία περιοδικού: Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE
Imprint Name(s): Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.
Ιατρικοί όροι (MeSH): Myocytes, Cardiac*/drug effects , Myocytes, Cardiac*/enzymology , Myocytes, Cardiac*/metabolism , Protein Biosynthesis*/drug effects , Protein Biosynthesis*/physiology , Extracellular Signal-Regulated MAP Kinases*/metabolism , MAP Kinase Signaling System*/physiology , MAP Kinase Signaling System*/drug effects , Single Molecule Imaging*/methods, Microtubules/metabolism ; Animals ; Rats ; Rats, Sprague-Dawley ; Cells, Cultured ; Male
Περίληψη: Background: Translational control of gene expression is crucial in cardiomyocytes, particularly in response to hypertrophic stimuli. The ERK (extracellular signal-regulated kinase) pathway plays a key role in inducing cardiac hypertrophy and regulating specific protein translation. However, it remains unclear how this specificity is achieved, and the spatiotemporal regulation of protein translation is not fully understood.
Methods: We used SINAP (single-molecule imaging of nascent peptide) reporters to visualize and analyze the translation dynamics in single adult rat ventricular cardiomyocytes and tracked active translation sites at high spatiotemporal resolution. We also examined the effects of adrenergic stimulation and the role of the ERK pathway in translation localization.
Results: Our findings revealed that translation sites are primarily localized near Z-lines in cardiomyocytes, with some sites being highly dynamic and moving during translation. The 3' untranslated regions did not significantly change the localization of translation. Many translation sites colocalized with microtubules, and their movement predominantly occurred along microtubular tracks. Adrenergic stimulation led to a transient shift in translation activity toward the perinuclear region, peaking at 12 hours and requiring ERK pathway activity for this localization change. This shift is part of the hypertrophic response and is required for early translation of genes such as Nppa.
Conclusions: Our high-resolution single-cell study demonstrates that protein translation in cardiomyocytes is dynamic and responsive to hypertrophic stimuli in an ERK-dependent manner. The localized translation mechanism allows cardiomyocytes to rapidly adapt to changing environments by preferentially translating mRNAs in the perinuclear region. These findings provide new insights into the spatial regulation of translation in cardiomyocytes and its role in cardiac hypertrophy.
Competing Interests: None.
Contributed Indexing: Keywords: extracellular signal-regulated MAP kinases; hypertrophy; microtubules; myocytes, cardiac; protein biosynthesis
Substance Nomenclature: EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
Entry Date(s): Date Created: 20260821 Date Completed: 20260924 Latest Revision: 20260924
Update Code: 20260925
DOI: 10.1161/CIRCRESAHA.126.329033
PMID: 42626779
Βάση Δεδομένων: MEDLINE