The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to α-synuclein toxicity in Parkinson's disease models.
The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to α-synuclein toxicity in Parkinson's disease models.
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DOI：
10.1038/cdd.2012.142
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发表时间：
2013-03
影响因子：
12.4
通讯作者：
中科院分区：
文献类型：
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作者：
Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, which arises from a yet elusive concurrence between genetic and environmental factors. The protein α-synuclein (αSyn), the principle toxic effector in PD, has been shown to interfere with neuronal Ca2+ fluxes, arguing for an involvement of deregulated Ca2+ homeostasis in this neuronal demise. Here, we identify the Golgi-resident Ca2+/Mn2+ ATPase PMR1 (plasma membrane-related Ca2+-ATPase 1) as a phylogenetically conserved mediator of αSyn-driven changes in Ca2+ homeostasis and cytotoxicity. Expression of αSyn in yeast resulted in elevated cytosolic Ca2+ levels and increased cell death, both of which could be inhibited by deletion of PMR1. Accordingly, absence of PMR1 prevented αSyn-induced loss of dopaminergic neurons in nematodes and flies. In addition, αSyn failed to compromise locomotion and survival of flies when PMR1 was absent. In conclusion, the αSyn-driven rise of cytosolic Ca2+ levels is pivotal for its cytotoxicity and requires PMR1.
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DOI：
10.1083/jcb.200203052
发表时间：
2002-06-10
期刊：
The Journal of cell biology
影响因子：
--
作者：
Cronin SR;Rao R;Hampton RY
通讯作者：
Hampton RY
影响因子：
3.7
作者：
Clark J;Clore EL;Zheng K;Adame A;Masliah E;Simon DK
通讯作者：
Simon DK
影响因子：
4.7
作者：
Hettiarachchi, Nishani T.;Parker, Andrew;Peers, Chris
通讯作者：
Peers, Chris
影响因子：
4.3
作者：
Jomova, Klaudia;Vondrakova, Dagmar;Valko, Marian
通讯作者：
Valko, Marian
影响因子：
64.8
作者：
Chan, C. Savio;Guzman, Jaime N.;Surmeier, D. James
通讯作者：
Surmeier, D. James