Balasanyan Varuzhan, Arnold Don B
Department of Biology, Program in Molecular and Computational Biology, University of Southern California, Los Angeles, California, United States of America.
PLoS One. 2014 Mar 17;9(3):e92349. doi: 10.1371/journal.pone.0092349. eCollection 2014.
The localization of mRNAs within axons and dendrites allows neurons to manipulate protein levels in a time and location dependent manner and is essential for processes such as synaptic plasticity and axon guidance. However, an essential step in the process of mRNA localization, the decision to traffic to dendrites and/or axons, remains poorly understood. Here we show that Myosin Va and actin filaments are necessary for the dendritic localization of the mRNA binding protein Staufen 1 and of mRNA encoding the microtubule binding protein Map2. Blocking the function or expression of Myosin Va or depolymerizing actin filaments leads to localization of Staufen 1 and of Map2 mRNA in both axons and dendrites. Furthermore, interaction with Myosin Va plays an instructive role in the dendritic localization of Hermes 1, an RNA binding protein. Wild-type Hermes 1 localizes to both axons and dendrites, whereas Hermes 1 fused with a Myosin Va binding peptide, localizes specifically to dendrites. Thus, our results suggest that targeting of mRNAs to the dendrites is mediated by a mechanism that is dependent on actin and Myosin Va.
信使核糖核酸（mRNA）在轴突和树突内的定位使神经元能够以时间和位置依赖的方式调控蛋白质水平，这对于诸如突触可塑性和轴突导向等过程至关重要。然而，mRNA定位过程中的一个关键步骤，即决定向树突和/或轴突运输，仍知之甚少。在此，我们表明肌球蛋白Va和肌动蛋白丝对于mRNA结合蛋白Staufen 1以及编码微管结合蛋白Map2的mRNA的树突定位是必需的。阻断肌球蛋白Va的功能或表达，或使肌动蛋白丝解聚，会导致Staufen 1和Map2 mRNA在轴突和树突中均出现定位。此外，与肌球蛋白Va的相互作用在RNA结合蛋白Hermes 1的树突定位中起指导作用。野生型Hermes 1定位于轴突和树突，而与肌球蛋白Va结合肽融合的Hermes 1则特异性定位于树突。因此，我们的结果表明，mRNA靶向树突是由一种依赖于肌动蛋白和肌球蛋白Va的机制介导的。
