Sofola Oyinkan, Sundram Vasudha, Ng Fanny, Kleyner Yelena, Morales Joannella, Botas Juan, Jackson F Rob, Nelson David L
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
J Neurosci. 2008 Oct 8;28(41):10200-5. doi: 10.1523/JNEUROSCI.2786-08.2008.
Fragile X syndrome (FXS) is the most common form of hereditary mental retardation. FXS patients have a deficit for the fragile X mental retardation protein (FMRP) that results in abnormal neuronal dendritic spine morphology and behavioral phenotypes, including sleep abnormalities. In a Drosophila model of FXS, flies lacking the dfmr1 protein (dFMRP) have abnormal circadian rhythms apparently as a result of altered clock output. In this study, we present biochemical and genetic evidence that dFMRP interacts with a known clock output component, the LARK RNA-binding protein. Our studies demonstrate physical interactions between dFMRP and LARK, that the two proteins are present in a complex in vivo, and that LARK promotes the stability of dFMRP. Furthermore, we show genetic interactions between the corresponding genes indicating that dFMRP and LARK function together to regulate eye development and circadian behavior.
脆性X综合征（FXS）是遗传性智力障碍最常见的形式。FXS患者缺乏脆性X智力障碍蛋白（FMRP），这导致神经元树突棘形态异常和行为表型异常，包括睡眠异常。在FXS的果蝇模型中，缺乏dfmr1蛋白（dFMRP）的果蝇具有异常的昼夜节律，这显然是由于生物钟输出改变所致。在本研究中，我们提供了生化和遗传学证据，证明dFMRP与已知的生物钟输出成分LARK RNA结合蛋白相互作用。我们的研究表明dFMRP与LARK之间存在物理相互作用，这两种蛋白在体内存在于一个复合物中，并且LARK促进dFMRP的稳定性。此外，我们展示了相应基因之间的遗传相互作用，表明dFMRP和LARK共同发挥作用来调节眼睛发育和昼夜行为。
