Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homoeostasis
Bidirectional regulation of fragile X mental retardation protein phosphorylation controls rhodopsin homoeostasis
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DOI：
10.1093/jmcb/mjw041
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发表时间：
2017-04
影响因子：
5.5
通讯作者：
Xiao Wang;Yawen Mu;Mengshi Sun;Junhai Han
中科院分区：
文献类型：
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作者：
Xiao Wang;Yawen Mu;Mengshi Sun;Junhai Han
光感受器视紫红质的恒稳态调节对于维持光敏感性和光感受器的存活至关重要。主要的果蝇视紫红质，Rh 1，经历光诱导的内吞和降解，但其蛋白质和mRNA水平保持恒定，在光/暗周期。目前尚不清楚Rh 1的翻译是如何调节的。在这里，我们表明，成人光感受器保持恒定的，丰富的ninaE mRNA，编码Rh 1。我们证明，Fmr 1蛋白与ninaE mRNA和抑制其翻译。此外，光暴露触发Fmr 1的钙依赖性去磷酸化，从而缓解Rh 1翻译的抑制。我们证明，Mts，蛋白磷酸酶2A（PP 2A）的催化亚基，介导光诱导的Fmr 1去磷酸化的调节B亚基的PP 2A（CKa）依赖性的方式。最后，我们表明，阻止光诱导的Rh 1翻译的结果降低光敏感性。我们的研究结果揭示了Rh 1稳态的分子机制和Rh 1失调的生理后果。
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.