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Cooper, A.A., Gitler, A.D., Cashikar, A., Haynes, C.M., Hill, K.J., Bhullar, B., Liu, K., Xu, K., Strathearn, K.E., Liu, F., Cao, S., Caldwell, K.A., Caldwell, G.A., Marsischky, G., Kolodner, R.D., Labaer, J., Rochet, J.C., Bonini, N.M., Lindquist, S. (2006). Alpha-synuclein blocks ER-Golgi traffic and Rab1 rescues neuron loss in Parkinson's models.  Science 313(5785): 324--328.
FlyBase ID
FBrf0205615
Publication Type
Research paper
Abstract

Alpha-synuclein (alphaSyn) misfolding is associated with several devastating neurodegenerative disorders, including Parkinson's disease (PD). In yeast cells and in neurons alphaSyn accumulation is cytotoxic, but little is known about its normal function or pathobiology. The earliest defect following alphaSyn expression in yeast was a block in endoplasmic reticulum (ER)-to-Golgi vesicular trafficking. In a genomewide screen, the largest class of toxicity modifiers were proteins functioning at this same step, including the Rab guanosine triphosphatase Ypt1p, which associated with cytoplasmic alphaSyn inclusions. Elevated expression of Rab1, the mammalian YPT1 homolog, protected against alphaSyn-induced dopaminergic neuron loss in animal models of PD. Thus, synucleinopathies may result from disruptions in basic cellular functions that interface with the unique biology of particular neurons to make them especially vulnerable.

PubMed ID
PubMed Central ID
PMC1983366 (PMC) (EuropePMC)
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    Language of Publication
    English
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    Publication Type
    Journal
    Abbreviation
    Science
    Title
    Science
    Publication Year
    1895-
    ISBN/ISSN
    0036-8075
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    Alleles (4)
    Genes (4)
    Human Disease Models (1)
    Natural transposons (1)
    Experimental Tools (1)
    Transgenic Constructs (4)