The interaction between calcineurin and α-synuclein is regulated by calcium and calmodulin

Biochem Biophys Res Commun. 2018 Feb 19;496(4):1109-1114. doi: 10.1016/j.bbrc.2018.01.148. Epub 2018 Feb 7.

Abstract

Calcineurin (CN) is a protein phosphatase and widely distributed in eukaryotes, with an extremely high level of expression in mammalian brain. Alpha-synuclein (α-syn) is a small soluble protein expressed primarily at presynaptic terminals in the central nervous system. In our present study, we explored the interactions between CN and α-syn in vitro. Based on the data from microscale thermophoresis, GST pull-down assays, and co-immunoprecipitation, we found that CN binds α-syn. Furthermore, this interaction is mediated by calcium/calmodulin (Ca2+/CaM) signaling. Additionally, thapsigargin (TG) triggered an increase in CN activity and α-syn aggregation in HEK293 cells stably transfected with α-syn. Our previous study in vivo suggest that overexpression of α-syn in transgenic mice significantly promoted CN activity and subsequent nuclear translocation of nuclear factor of activated T-cells (NFAT) in the midbrain dopaminergic (mDA) neurons. These in vivo and in vitro studies have been complementary with each other, representing the changes in the CN-dependent pathway affected by overexpression of α-syn.

Keywords: Alpha-synuclein; Calcineurin; Co-immunoprecipitation; GST pull-down assays; Microscale thermophoresis; Thapsigargin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcineurin / metabolism*
  • Calcium / metabolism*
  • Calmodulin / metabolism*
  • Gene Expression Regulation / physiology*
  • HEK293 Cells
  • Humans
  • Protein Binding
  • Protein Interaction Mapping
  • Signal Transduction / physiology*
  • alpha-Synuclein / metabolism*

Substances

  • Calmodulin
  • alpha-Synuclein
  • Calcineurin
  • Calcium