Journal
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
Volume 116, Issue -, Pages 16-28Publisher
ELSEVIER SCI LTD
DOI: 10.1016/j.yjmcc.2018.01.012
Keywords
Sarcomere; mRNA localization; Localized synthesis; Ubiquitin proteasome
Categories
Funding
- Jiangsu Provincial Natural Science Foundation of China [BK20151146]
- National Key Research and Development Program [2016YFC0600905]
- National Natural Science Foundation of China [51575513, U1510205]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
- Rappaport Family Institute for Research in the Medical Sciences
- Clinical Research Institute at Rambam, Rambam Medical Center
- Israel Science Foundation [1424/16, 2243/17]
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The mechanisms responsible for maintaining macromolecular protein complexes, with their proper localization and subunit stoichiometry, are incompletely understood. Here we studied the maintenance of the sarcomere, the basic contractile macromolecular complex of cardiomyocytes. We performed single-cell analysis of cardiomyocytes using imaging of mRNA and protein synthesis, and demonstrate that three distinct mechanisms are responsible for the maintenance of the sarcomere: mRNAs encoding for sarcomeric proteins are localized to the sarcomere, ribosomes are localized to the sarcomere with localized sarcomeric protein translation, and finally, a localized E3 ubiquitin ligase allow efficient degradation of excess unincorporated sarcomeric proteins. We show that these mechanisms are distinct, required, and work in unison, to ensure both spatial localization, and to overcome the large variability in transcription. Cardiomyocytes simultaneously maintain all their sarcomeres using localized translation and degradation processes where proteins are continuously and locally synthesized at high rates, and excess proteins are continuously degraded.
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