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

• Published in: iScience Vol. 19; pp. 291 - 302
• Main Authors: Guo, Pengfei, Xu, Xiao, Wang, Fang, Yuan, Xin, Tu, Yinqi, Zhang, Bei, Zheng, Huimei, Yu, Danqing, Ge, Wanzhong, Gong, Zhefeng, Yang, Xiaohang, Xi, Yongmei
• Format: Journal Article
• Language: English
• Published: Elsevier Inc 27.09.2019; Elsevier
• Subjects: Molecular Genetics; Molecular Neuroscience; Molecular Neuroscience; Molecular Genetics
• ISSN: 2589-0042; 2589-0042
• DOI: 10.1016/j.isci.2019.07.026

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. [Display omitted] •PRL-1 functions to protect the nervous system against olfactory CO2 stimulation•PRL-1 physically interacts with Uex and controls Uex expression levels•PRLs may retain a similar neuroprotective function in humans Molecular Genetics; Molecular Neuroscience