A Novel Neuroprotective Role of Phosphatase of Regenerating Liver-1 against CO2 Stimulation in Drosophila.


Institute of Genetics and Department of Genetics, Division of Human Reproduction and Developmental Genetics of the Women's Hospital, Zhejiang University School of Medicine, Yuhangtang Road 866, Xihu District, Hangzhou, Zhejiang Province 310058, China; Joint Institute of Genetics and Genomic Medicine between Zhejiang University and University of Toronto, Zhejiang University, Hangzhou, Zhejiang Province 310058, China. Electronic address: [Email]


Neuroprotection is essential for the maintenance of normal physiological functions in the nervous system. This is especially true under stress conditions. Here, we demonstrate a novel protective function of PRL-1 against CO2 stimulation in Drosophila. In the absence of PRL-1, flies exhibit a permanent held-up wing phenotype upon CO2 exposure. Knockdown of the CO2 olfactory receptor, Gr21a, suppresses the phenotype. Our genetic data indicate that the wing phenotype is due to a neural dysfunction. PRL-1 physically interacts with Uex and controls Uex expression levels. Knockdown of Uex alone leads to a similar wing held-up phenotype to that of PRL-1 mutants. Uex acts downstream of PRL-1. Elevated Uex levels in PRL-1 mutants prevent the CO2-induced phenotype. PRL-1 and Uex are required for a wide range of neurons to maintain neuroprotective functions. Expression of human homologs of PRL-1 could rescue the phenotype in Drosophila, suggesting a similar function in humans.


Molecular Genetics,Molecular Neuroscience,

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