Dysregulated CRMP Mediates Circadian Deficits in a Drosophila Model of Fragile X Syndrome  

作　　者：Juan Zhao Jin Xue Tengfei Zhu Hua He Huaixing Kang Xuan Jiang Wen Huang Ranhui Duan 

机构地区：[1]Center for Medical Genetics,School of Life Sciences,Central South University,Changsha 410078,China [2]Hunan Key Laboratory of Medical Genetics,Central South University,Changsha 410078,China [3]Hunan Key Laboratory of Animal Models for Human Diseases,Central South University,Changsha 410078,China

出　　处：《Neuroscience Bulletin》2021年第7期973-984,共12页神经科学通报（英文版）

基　　金：the Hunan Science and Technology major project of Birth Defect Cooperative Control(2019SK1010);the National Natural Science Foundation of China(81571253 and 81771385);the Hunan Provincial Natural Science Foundation(2016JJ3135);the Changsha Municipal Natural Science Foundation(kq2007073).

摘　　要：Fragile X syndrome(FXS)is the leading inherited cause of intellectual disability,resulting from the lack of functional fragile X mental retardation protein(FMRP),an mRNA binding protein mainly serving as a translational regulator.Loss of FMRP leads to dysregulation of target mRNAs.The Drosophila model of FXS show an abnormal circadian rhythm with disruption of the output pathway downstream of the clock network.Yet the FMRP targets involved in circadian regulation have not been identified.Here,we identified collapsing response mediator protein(CRMP)mRNA as a target of FMRP.Knockdown of pan-neuronal CRMP expression ameliorated the circadian defects and abnormal axonal structures of clock neurons(ventral lateral neurons)in dfmr1 mutant flies.Furthermore,specific reduction of CRMP in the downstream output insulin-producing cells attenuated the aberrant circadian behaviors.Molecular analyses revealed that FMRP binds with CRMP mRNA and negatively regulates its translation.Our results indicate that CRMP is an FMRP target and establish an essential role for CRMP in the circadian output in FXS Drosophila.

关 键 词：Fragile X syndrome FMRP CRMP Circadian rhythm 

分 类 号：R741[医药卫生—神经病学与精神病学]