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Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homoeostasis Free
Xiao Wang1, Yawen Mu1, Mengshi Sun1, and Junhai Han1,2,*
1 Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China
2 Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China *Correspondence to:Junhai Han, E-mail: junhaihan@seu.edu.cn
J Mol Cell Biol, Volume 9, Issue 2, April 2017, 104-116,  https://doi.org/10.1093/jmcb/mjw041
Keyword: G protein-coupled receptor, rhodopsin, fragile X mental retardation protein, dephosphorylation, calcium, protein phosphatase 2A

Homoeostatic regulation of the light sensor, rhodopsin, is critical for the maintenance of light sensitivity and survival of photoreceptors. The major fly rhodopsin, Rh1, undergoes light-induced endocytosis and degradation, but its protein and mRNA levels remain constant during light/dark cycles. It is not clear how translation of Rh1 is regulated. Here, we show that adult photoreceptors maintain a constant, abundant quantity of ninaE mRNA, which encodes Rh1. We demonstrate that the Fmr1 protein associates with ninaE mRNA and represses its translation. Further, light exposure triggers a calcium-dependent dephosphorylation of Fmr1, which relieves suppression of Rh1 translation. We demonstrate that Mts, the catalytic subunit of protein phosphatase 2A (PP2A), mediates light-induced Fmr1 dephosphorylation in a regulatory B subunit of PP2A (CKa)-dependent manner. Finally, we show that blocking light-induced Rh1 translation results in reduced light sensitivity. Our results reveal the molecular mechanism of Rh1 homoeostasis and physiological consequence of Rh1 dysregulation.