Kanai Yoshimitsu, Dohmae Naoshi, Hirokawa Nobutaka
Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Neuron. 2004 Aug 19;43(4):513-25. doi: 10.1016/j.neuron.2004.07.022.
RNA transport is an important and fundamental event for local protein synthesis, especially in neurons. RNA is transported as large granules, but little is known about them. Here, we isolated a large RNase-sensitive granule (size: 1000S approximately) as a binding partner of conventional kinesin (KIF5). We identified a total of 42 proteins with mRNAs for CaMKIIalpha and Arc in the granule. Seventeen of the proteins (hnRNP-U, Pur alpha and beta, PSF, DDX1, DDX3, SYNCRIP, TLS, NonO, HSPC117, ALY, CGI-99, staufen, three FMRPs, and EF-1alpha) were extensively investigated, including their classification, binding combinations, and necessity for the "transport" of RNA. These proteins and the mRNAs were colocalized to the kinesin-associated granules in dendrites. The granules moved bidirectionally, and the distally directed movement was enhanced by the overexpression of KIF5 and reduced by its functional blockage. Thus, kinesin transports RNA via this granule in dendrites coordinately with opposite motors, such as dynein.
RNA转运是局部蛋白质合成过程中的一个重要且基础的事件，在神经元中尤为如此。RNA以大颗粒的形式进行转运，但人们对这些颗粒了解甚少。在此，我们分离出一种对RNase敏感的大颗粒（大小：约1000S），作为传统驱动蛋白（KIF5）的结合伴侣。我们在该颗粒中鉴定出总共42种与CaMKIIα和Arc的mRNA相关的蛋白质。对其中17种蛋白质（hnRNP-U、Purα和β、PSF、DDX1、DDX3、SYNCRIP、TLS、NonO、HSPC117、ALY、CGI-99、staufen、三种FMRP和EF-1α）进行了广泛研究，包括它们的分类、结合组合以及RNA“转运”的必要性。这些蛋白质和mRNA共定位于树突中与驱动蛋白相关的颗粒上。颗粒双向移动，KIF5的过表达增强了向远端的移动，而其功能阻断则使其减弱。因此，驱动蛋白通过这种颗粒在树突中与诸如动力蛋白等相反方向的马达协同转运RNA。
