title: Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homoeostasis.
abstract: 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.
authors.affiliation: Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.affiliation: Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
authors.forename: Yawen
authors.initials: Y
authors.lastname: Mu
authors.affiliation: Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.
authors.forename: Mengshi
authors.initials: M
authors.lastname: Sun
authors.affiliation: Institute of Life Sciences, The Key Laboratory of Developmental Genes and Human Disease, Southeast University, Nanjing 210096, China.|Co-innovation Center of Neuroregeneration, Nantong University, Nantong 226001, China.
authors.forename: Junhai
authors.initials: J
authors.lastname: Han
mesh_terms: D000375:Aging / Q000378:metabolism; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000378:metabolism* / Q000528:radiation effects; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000378:metabolism*; D006706:Homeostasis / Q000528:radiation effects; D008027:Light; D055537:Light Signal Transduction / Q000528:radiation effects; D010766:Phosphorylation / Q000528:radiation effects; D017956:Photoreceptor Cells, Invertebrate / Q000378:metabolism / Q000528:radiation effects; D014176:Protein Biosynthesis / Q000528:radiation effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D029721:Drosophila Proteins; D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; D012243:Rhodopsin; C083315:ninaE protein, Drosophila
keywords: G protein-coupled receptor; calcium; dephosphorylation; fragile X mental retardation protein; protein phosphatase 2A; rhodopsin