Non-excitable cells express sodium voltage-gated channel alpha subunit 1 gene and protein (SCN1A/NaV1.1); however, the functions of NaV1.1 are unclear. SCN1A was expressed in human mesenchymal stem cells (MSCs). Nav1.1 was abundantly expressed in the endoplasmic reticulum of MSCs; however, its expression was not found to be related to sodium currents. SCN1A-silencing reduced MSC proliferation and delayed the cell cycle in the S phase. SCN1A-silencing also suppressed the protein levels of CDK2 and AKT, despite similar mRNA expression, and inhibited AKT phosphorylation in MSCs. Cycloheximide-chase assay showed that SCN1A-silencing induced CDK2 but not AKT protein degradation in MSCs. Proteolysis inhibition assay using epoxomicin, bafilomycin A1, and NH4Cl, revealed that the ubiquitin-proteasome and autophagy/endo-lysosome systems were irrelevant to CDK2 and AKT protein reduction in SCN1A-silenced MSCs. AKT inhibitor LY294002 did not affect the degradation and nuclear localization of CDK2 in MSCs. Likewise, AKT activator SC79 did not attenuate the SCN1A-silencing effects on CDK2 in MSCs. These results suggest that NaV1.1 contributes to the cell cycle of MSCs by regulating the post-translational control of AKT and CDK2.
NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2
These authors contributed equally to the work
- Award Group:
- Funder(s): Japan Society for the Promotion of Science
- Award Id(s): JP22K10275
- Funder(s):
- Award Group:
- Funder(s): UBE Industries Foundation
- Funder(s):
- Award Group:
- Funder(s): Takeda Science Foundation
- Funder(s):
- Award Group:
- Funder(s): The Japan Epilepsy Research Foundation
- Funder(s):
Mohammed Fouad Zakaria, Hiroki Kato, Soichiro Sonoda, Kenichi Kato, Norihisa Uehara, Yukari Kyumoto-Nakamura, Mohammed Majd Sharifa, Liting Yu, Lisha Dai, Haruyoshi Yamaza, Shunichi Kajioka, Fusanori Nishimura, Takayoshi Yamaza; NaV1.1 contributes to the cell cycle of human mesenchymal stem cells by regulating AKT and CDK2. J Cell Sci 2024; jcs.261732. doi: https://doi.org/10.1242/jcs.261732
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