Mitsumori Kazuhiko, Takei Yosuke, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan.
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-0033, Japan
Mol Biol Cell. 2017 Jun 1;28(11):1412-1417. doi: 10.1091/mbc.E16-07-0497. Epub 2017 Apr 12.
In neurons, RNA transport is important for local protein synthesis. mRNAs are transported along dendrites as large RNA granules. The localization and dynamics of Puralpha and Staufen1 (Stau1), major components of RNA transport granules, were investigated in cultured hippocampal neurons. Puralpha-positive granules were localized in both the shafts and spines of dendrites. In contrast, Stau1-positive granules tended to be localized mainly in dendritic shafts. More than 90% of Puralpha-positive granules were positive for Stau1 in immature dendrites, while only half were positive in mature dendrites. Stau1-negative Puralpha granules tended to be stationary with fewer anterograde and retrograde movements than Stau1-positive Puralpha granules. After metabotropic glutamate receptor 5 activation, Stau1-positive granules remained in the dendritic shafts, while Puralpha granules translocated from the shaft to the spine. The translocation of Puralpha granules was dependent on myosin Va, an actin-based molecular motor protein. Collectively our findings suggest the possibility that the loss of Stau1 in Puralpha-positive RNA granules might promote their activity-dependent translocation into dendritic spines, which could underlie the regulation of protein synthesis in synapses.
在神经元中,RNA运输对于局部蛋白质合成很重要。mRNA作为大的RNA颗粒沿树突运输。在培养的海马神经元中研究了RNA运输颗粒的主要成分Puralpha和Staufen1(Stau1)的定位和动力学。Puralpha阳性颗粒定位于树突的轴和棘中。相比之下,Stau1阳性颗粒倾向于主要定位于树突轴中。在未成熟树突中,超过90%的Puralpha阳性颗粒对Stau1呈阳性,而在成熟树突中只有一半呈阳性。与Stau1阳性的Puralpha颗粒相比,Stau1阴性的Puralpha颗粒倾向于静止,顺行和逆行运动较少。代谢型谷氨酸受体5激活后,Stau1阳性颗粒保留在树突轴中,而Puralpha颗粒从轴转移到棘。Puralpha颗粒的转移依赖于肌球蛋白Va,一种基于肌动蛋白的分子运动蛋白。我们的研究结果共同表明,Puralpha阳性RNA颗粒中Stau1的缺失可能会促进其活性依赖性转移到树突棘中,这可能是突触中蛋白质合成调控的基础。