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
• 来源期刊: 神经科学通报（英文版）
• 年，卷（期）: 2021,（7）
• 所属期刊栏目: Original Articles
• 页码范围: 973-984
• 页数: 12页
• 语种: 英文

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 dysregula-tion 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 circa-dian defects and abnormal axonal structures of clock neurons(ventral lateral neurons)in dfmr1 mutant flies.Furthermore,specific reduction of CRMP in the down-stream output insulin-producing cells attenuated the aber-rant 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.