An elongated tract of polyQ in the carboxyl‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation
- Ji Sun
- Xiguang Sun
- Zhuo Li
- Dihui Ma
- Yudan Lv
Affiliations: Department of Pediatric Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Hand Surgery, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China, Department of Neurology, The First Hospital of Jilin University, Changchun, Jilin 130021, P.R. China
- Published online on: April 22, 2020 https://doi.org/10.3892/or.2020.7592
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An aberrant elongated tract of glutamine residues (polyQ) in proteins induces multiple diseases treated in the clinic. In our previous study of progressive myoclonic epilepsy (PME), using whole‑exome sequencing, a mutant Cav2.1 protein with an aberrant elongated polyQ tract was identified in PME patients. To investigate the molecular mechanism and cell biology of this aberrant elongated polyQ tract, wild‑type Cav2.1 with 13 polyQ repeats (Cav2.1 wt‑Q13) and mutant‑type Cav2.1 with 26 polyQ repeats (Cav2.1 mt‑Q26) were prepared and introduced into human SH‑SY5Y neuroblastoma cells. Using a WST‑1 assay, it was revealed that Cav2.1 mt‑Q26 markedly suppressed the proliferation of the SH‑SY5Y cells, a result not observed for the Cav2.1 wt‑Q13‑transfected cells. It was also revealed that Cav2.1 mt and its truncated molecules suppressed cell proliferation by inducing apoptosis rather than arresting the cell cycle. Further investigations indicated a nuclear translocation phenomenon associated with the Cav2.1 mt molecules. Mechanistically, it was revealed that the Cav2.1 mt molecules activated the Bcl‑2/Bax, caspase‑3 and poly ADP‑ribose polymerase (PARP) apoptotic pathways. The present study may provide new insights for interpreting the pathogenesis of PME and the relationship among polyQ, CACNA1A gene mutations and PME.