PMID- 29409956 OWN - NLM STAT- MEDLINE DCOM- 20180322 LR - 20180322 IS - 1090-2104 (Electronic) IS - 0006-291X (Linking) VI - 496 IP - 4 DP - 2018 Feb 19 TI - The interaction between calcineurin and alpha-synuclein is regulated by calcium and calmodulin. PG - 1109-1114 LID - S0006-291X(18)30169-4 [pii] LID - 10.1016/j.bbrc.2018.01.148 [doi] AB - Calcineurin (CN) is a protein phosphatase and widely distributed in eukaryotes, with an extremely high level of expression in mammalian brain. Alpha-synuclein (alpha-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 alpha-syn in vitro. Based on the data from microscale thermophoresis, GST pull-down assays, and co-immunoprecipitation, we found that CN binds alpha-syn. Furthermore, this interaction is mediated by calcium/calmodulin (Ca(2+)/CaM) signaling. Additionally, thapsigargin (TG) triggered an increase in CN activity and alpha-syn aggregation in HEK293 cells stably transfected with alpha-syn. Our previous study in vivo suggest that overexpression of alpha-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 alpha-syn. CI - Copyright (c) 2018 Elsevier Inc. All rights reserved. FAU - Shi, Xiaoyu AU - Shi X AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China; College of Life Sciences, Langfang Normal University, Hebei, 065000, China. FAU - Sun, Yue AU - Sun Y AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Wang, Ping AU - Wang P AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Gu, Lingling AU - Gu L AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Wang, Lu AU - Wang L AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Yang, Huan AU - Yang H AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Wei, Qun AU - Wei Q AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. FAU - Li, Zhimei AU - Li Z AD - Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, China National Clinical Research Center for Neurological Diseases, Beijing 100050, China. Electronic address: lizm1211@163.com. FAU - Luo, Jing AU - Luo J AD - Gene Engineering and Biotechnology, Beijing Key Laboratory, College of Life Sciences, Beijing Normal University, No.19, Xinjiekouwaidajie, Beijing 100875, China. Electronic address: luojing@bnu.edu.cn. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180207 PL - United States TA - Biochem Biophys Res Commun JT - Biochemical and biophysical research communications JID - 0372516 RN - 0 (Calmodulin) RN - 0 (alpha-Synuclein) RN - EC 3.1.3.16 (Calcineurin) RN - SY7Q814VUP (Calcium) SB - IM MH - Calcineurin/*metabolism MH - Calcium/*metabolism MH - Calmodulin/*metabolism MH - Gene Expression Regulation/*physiology MH - HEK293 Cells MH - Humans MH - Protein Binding MH - Protein Interaction Mapping MH - Signal Transduction/*physiology MH - alpha-Synuclein/*metabolism OTO - NOTNLM OT - Alpha-synuclein OT - Calcineurin OT - Co-immunoprecipitation OT - GST pull-down assays OT - Microscale thermophoresis OT - Thapsigargin EDAT- 2018/02/08 06:00 MHDA- 2018/03/23 06:00 CRDT- 2018/02/08 06:00 PHST- 2018/01/16 00:00 [received] PHST- 2018/01/24 00:00 [accepted] PHST- 2018/02/08 06:00 [pubmed] PHST- 2018/03/23 06:00 [medline] PHST- 2018/02/08 06:00 [entrez] AID - S0006-291X(18)30169-4 [pii] AID - 10.1016/j.bbrc.2018.01.148 [doi] PST - ppublish SO - Biochem Biophys Res Commun. 2018 Feb 19;496(4):1109-1114. doi: 10.1016/j.bbrc.2018.01.148. Epub 2018 Feb 7.