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Resources » Paper

Buttner S et al. (2013) Cell Death Differ "The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to -synuclein toxicity in Parkinson's disease models."

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  • Comments on Buttner S et al. (2013) Cell Death Differ "The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to -synuclein toxicity in Parkinson's disease models." (0)

  • Overview

    PMID:
    23154387
    DOI:
    10.1038/cdd.2012.142
    Status:
    Publication type:
    Journal_article
    WormBase ID:
    WBPaper00048828

    Buttner S, Faes L, Reichelt WN, Broeskamp F, Habernig L, Benke S, Kourtis N, Ruli D, Carmona-Gutierrez D, Eisenberg T, D'hooge P, Ghillebert R, Franssens V, Harger A, Pieber TR, Freudenberger P, Kroemer G, Sigrist SJ, Winderickx J, Callewaert G, Tavernarakis N, & Madeo F (2013). The Ca2+/Mn2+ ion-pump PMR1 links elevation of cytosolic Ca(2+) levels to -synuclein toxicity in Parkinson's disease models. Cell Death Differ, 20, 465-77. doi:10.1038/cdd.2012.142

    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 -synuclein (Syn), the principle toxic effector in PD, has been shown to interfere with neuronal Ca(2+) fluxes, arguing for an involvement of deregulated Ca(2+) homeostasis in this neuronal demise. Here, we identify the Golgi-resident Ca(2+)/Mn(2+) ATPase PMR1 (plasma membrane-related Ca(2+)-ATPase 1) as a phylogenetically conserved mediator of Syn-driven changes in Ca(2+) homeostasis and cytotoxicity. Expression of Syn in yeast resulted in elevated cytosolic Ca(2+) levels and increased cell death, both of which could be inhibited by deletion of PMR1. Accordingly, absence of PMR1 prevented Syn-induced loss of dopaminergic neurons in nematodes and flies. In addition, Syn failed to compromise locomotion and survival of flies when PMR1 was absent. In conclusion, the Syn-driven rise of cytosolic Ca(2+) levels is pivotal for its cytotoxicity and requires PMR1.

    Authors: Buttner S, Faes L, Reichelt WN, Broeskamp F, Habernig L, Benke S, Kourtis N, Ruli D, Carmona-Gutierrez D, Eisenberg T, D'hooge P, Ghillebert R, Franssens V, Harger A, Pieber TR, Freudenberger P, Kroemer G, Sigrist SJ, Winderickx J, Callewaert G, Tavernarakis N, Madeo F


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