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Citation
Wang, Z., Ferdousy, F., Lawal, H., Huang, Z., Daigle, J.G., Izevbaye, I., Doherty, O., Thomas, J., Stathakis, D.G., O'Donnell, J.M. (2011). Catecholamines up integrates dopamine synthesis and synaptic trafficking.  J. Neurochem. 119(6): 1294--1305.
FlyBase ID
FBrf0216854
Publication Type
Research paper
Abstract

The highly reactive nature of dopamine renders dopaminergic neurons vulnerable to oxidative damage. We recently demonstrated that loss-of-function mutations in the Drosophila gene Catecholamines up (Catsup) elevate dopamine pools but, paradoxically, also confer resistance to paraquat, an herbicide that induces oxidative stress-mediated toxicity in dopaminergic neurons. We now report a novel association of the membrane protein, Catsup, with GTP cyclohydrolase rate-limiting enzyme for tetrahydrobiopterin (BH(4)) biosynthesis and tyrosine hydroxylase, rate-limiting enzyme for dopamine biosynthesis, which requires BH(4) as a cofactor. Loss-of-function Catsup mutations cause dominant hyperactivation of both enzymes. Elevated dopamine levels in Catsup mutants coincide with several distinct characteristics, including hypermobility, minimal basal levels of 3,4-dihydroxy-phenylacetic acid, an oxidative metabolite of dopamine, and resistance to the vesicular monoamine transporter inhibitor, reserpine, suggesting that excess dopamine is synaptically active and that Catsup functions in the regulation of synaptic vesicle loading and release of dopamine. We conclude that Catsup regulates and links the dopamine synthesis and transport networks.

PubMed ID
PubMed Central ID
PMC3233821 (PMC) (EuropePMC)
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Secondary IDs
    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    J. Neurochem.
    Title
    Journal of Neurochemistry
    Publication Year
    1956-
    ISBN/ISSN
    0022-3042
    Data From Reference
    Alleles (5)
    Genes (5)
    Physical Interactions (4)
    Natural transposons (1)
    Experimental Tools (2)
    Transgenic Constructs (2)