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The cell-wide web coordinates cellular processes by directing site-specific Ca2+ flux across cytoplasmic nanocourses

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Original languageEnglish
Article number2299
JournalNature Communications
Issue number1
Early online date24 May 2019
Publication statusPublished - 24 May 2019


Ca2+ coordinates diverse cellular processes, yet how function-specific signals arise is enigmatic. We describe a cell-wide network of distinct cytoplasmic nano courses with the nucleus at its centre, demarcated by sarcoplasmic reticulum (SR) junctions (≤400 nm across) that restrict Ca2+ diffusion and by nanocourse-specific Ca2+-pumps that facilitate signal segregation. Ryanodine receptor subtype 1 (RyR1) supports relaxation of arterial myocytes by unloading Ca2+ into peripheral nanocourses delimited by plasmalemma-SR junctions, fed bysarco/endoplasmic reticulum Ca2+ ATPase 2b (SERCA2b). Conversely, stimulus-specified increases in Ca2+ flux through RyR2/3 clusters selects for rapid propagation of Ca2+ signals throughout deeper extra perinuclear nanocourses and thus myocyte contraction. Nuclear envelope invaginations incorporating SERCA1 in their outer nuclear membranes demarcate further diverse networks of cytoplasmic nano courses that receive Ca2+ signals through discrete RyR1 clusters, impacting gene expression through epigenetic marks segregated by their associated invaginations. Critically, this circuit is not hardwired and remodels for different outputs during cell proliferation.

    Research areas

  • Animals, Calcium Signaling/physiology, Cell Membrane/metabolism, Cell Proliferation/physiology, Cells, Cultured, Cytosol/metabolism, Male, Muscle Cells/physiology, Muscle Contraction/physiology, Muscle, Skeletal/cytology, Nuclear Envelope/metabolism, Primary Cell Culture, Rats, Sprague-Dawley, Ryanodine Receptor Calcium Release Channel/metabolism, Sarcoplasmic Reticulum/metabolism, Sarcoplasmic Reticulum Calcium-Transporting ATPases/metabolism

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