Cell signalling
Can connexin43 work inside the nucleus?
Open access · cc by · source: Europe PMC
Cx43 sits at the nuclear envelope, enters via Importin-β, forms active nuclear channels in HEK293 cells and cardiomyocytes, and can change gene expression during myogenic differentiation.
Study at a glance
- Design
- Animal / in-vitro — Cell, tissue, and patch-clamp work showing Cx43 at the nuclear envelope of cultured cells and cardiac tissue
- N
- N=1 · Mechanistic study in HEK293 Cx43+ cells, adult primary cardiomyocytes, cardiomyoblasts, and cardiac tissue (not a clinical cohort)
- Population
- Cultured HEK293 cells, adult primary cardiomyocytes, cardiomyoblasts, and cardiac tissue
- Outcome
- Nuclear-envelope localization of Cx43, Importin-β-dependent translocation, nuclear channels, and transcriptome effects
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Key findings
Full-length Cx43 localizes to the nuclear envelope in multiple cell types and cardiac tissue. Nuclear entry needs Importin-β. Patch-clamp showed active nuclear-envelope channels, consistent with small-molecule nucleocytoplasmic shuttling. Nuclear Cx43 accumulates during cardiomyoblast differentiation.
Methodology
Used biochemistry, super-resolution and immunogold EM, Importin-β dependence tests, transcriptome readouts, and nuclear patch-clamp in HEK293 cells and adult primary cardiomyocytes.
Limitations
This is not a patient trial of a Cx43 drug; nuclear channel function in vivo human heart disease remains to be proven.
How this study connects
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