Animal cells and systems

The Korean Society for Integrative Biology (한국통합생물학회)
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[ ${\alpha}$ ]Synuclein Induces Unfolded Protein Response Via Distinct Signaling Pathway Independent of ER-membrane Kinases

  • Kang, Shin-Jung (Department of Molecular Biology, College of Natural Science, Sejong University) ;
  • Shin, Ki-Soon (Department of Biology, College of Science, Kyung Hee University) ;
  • Kim Kwon, Yun-Hee (Department of Biology, College of Science, Kyung Hee University)
  • Published : 2006.09.30
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Abstract

Parkinson's disease (PD) is a neurodegenerative disease caused by selective degeneration of dopaminergic neurons in the substantia nigra. Mutations in ${\alpha}$-synuclein have been causally linked to the pathogenesis of hereditary PD. In addition, it is a major component of Lewy body found in the brains of sporadic cases as well. In the present study, we examined whether overexpression of wild type or PD-related mutant ${\alpha}$-synuclein induces unfolded protein response (UPR) and triggers the known signaling pathway of the resulting endoplasmic reticulum (ER) stress in SH-SY5Y cells. Overexpression of wild type, A30P, and A53T ${\alpha}$-synuclein all induced XBP-1 mRNA splicing, one of the late stage UPR events. However, activation of ER membrane kinases and upregulation of ER or cytoplsmic chaperones were not detected when ${\alpha}$-synuclein was overexpressed. However, basal level of cytoplsmic calcium was elevated in ${\alpha}$-synuclein-expressing cells. Our observation suggests that overexpression of ${\alpha}$-synuclein induces UPR independent of the known ER membrane kinase-mediated signaling pathway and induces ER stress by disturbing calcium homeostasis.

Keywords

References

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