Antar L N, Dictenberg J B, Plociniak M, Afroz R, Bassell G J
Department of Neuroscience, Rose F. Kennedy Center for Mental Retardation, Albert Einstein College of Medicine, Bronx, NY 10461, USA.
Genes Brain Behav. 2005 Aug;4(6):350-9. doi: 10.1111/j.1601-183X.2005.00128.x.
Fragile X syndrome is caused by the absence of the fragile X mental-retardation protein (FMRP), an mRNA-binding protein, which may play important roles in the regulation of dendritic mRNA localization and/or synaptic protein synthesis. We have recently applied high-resolution fluorescence imaging methods to document the presence, motility and activity-dependent regulation of FMRP granule trafficking in dendrites and spines of cultured hippocampal neurons. In this study, we show that FMRP granules distribute to F-actin-rich compartments, including filopodia, spines and growth cones during the staged development of hippocampal neurons in culture. Fragile X mental-retardation protein granules were shown to colocalize with ribosomes, ribosomal RNA and MAP1B mRNA, a known FMRP target, which encodes a protein important for microtubule and actin stabilization. The levels of FMRP within dendrites were reduced by disruption of microtubule dynamics, but not by disruption of F-actin. Direct measurements of FMRP transport kinetics using fluorescence recovery after photobleaching in living neurons showed that microtubules were required to induce the mGluR-dependent translocation into dendrites. This study provides further characterization of the composition and regulated trafficking of FMRP granules in dendrites of hippocampal neurons.
脆性X综合征由脆性X智力低下蛋白（FMRP）缺失所致，FMRP是一种mRNA结合蛋白，可能在树突mRNA定位和/或突触蛋白合成的调控中发挥重要作用。我们最近应用高分辨率荧光成像方法记录了培养的海马神经元树突和棘中FMRP颗粒运输的存在、运动性及活性依赖性调控。在本研究中，我们发现，在培养的海马神经元的阶段性发育过程中，FMRP颗粒分布于富含F-肌动蛋白的区域，包括丝状伪足、棘和生长锥。脆性X智力低下蛋白颗粒与核糖体、核糖体RNA以及MAP1B mRNA（一种已知的FMRP靶标，编码对微管和肌动蛋白稳定很重要的一种蛋白质）共定位。树突内FMRP水平因微管动力学破坏而降低，但不因F-肌动蛋白破坏而降低。在活神经元中使用光漂白后荧光恢复直接测量FMRP转运动力学表明，微管是诱导mGluR依赖性转运进入树突所必需的。本研究进一步阐述了海马神经元树突中FMRP颗粒的组成和受调控的运输。
