Department of Microbiology, New York University School of Medicine, 550 First Ave., New York, NY 10016, USA; Institute of Pathology, University Medical Center, Johannes Gutenberg University, Langenbeckstrasse 1, D-55101 Mainz, Germany.
Sci Rep. 2011;1:140. doi: 10.1038/srep00140. Epub 2011 Nov 3.
Transport of mRNAs to diverse neuronal locations via RNA granules serves an important function in regulating protein synthesis within restricted sub-cellular domains. We recently detected the Huntington's disease protein huntingtin (Htt) in dendritic RNA granules; however, the functional significance of this localization is not known. Here we report that Htt and the huntingtin-associated protein 1 (HAP1) are co-localized with the microtubule motor proteins, the KIF5A kinesin and dynein, during dendritic transport of β-actin mRNA. Live cell imaging demonstrated that β-actin mRNA is associated with Htt, HAP1, and dynein intermediate chain in cultured neurons. Reduction in the levels of Htt, HAP1, KIF5A, and dynein heavy chain by lentiviral-based shRNAs resulted in a reduction in the transport of β-actin mRNA. These findings support a role for Htt in participating in the mRNA transport machinery that also contains HAP1, KIF5A, and dynein.
通过 RNA 颗粒将 mRNAs 运输到不同的神经元位置，在限制的细胞内区域内调节蛋白质合成方面发挥着重要作用。我们最近在树突状 RNA 颗粒中检测到亨廷顿病蛋白 httn（Htt）；然而，这种定位的功能意义尚不清楚。在这里，我们报告说 Htt 和 Huntingtin 相关蛋白 1（HAP1）在β-肌动蛋白 mRNA 的树突状运输过程中与微管马达蛋白 KIF5A 驱动蛋白和动力蛋白共定位。活细胞成像显示，β-肌动蛋白 mRNA 与 Htt、HAP1 和动力蛋白中间链在培养神经元中相关。基于慢病毒的 shRNA 降低 Htt、HAP1、KIF5A 和动力蛋白重链的水平导致β-肌动蛋白 mRNA 的运输减少。这些发现支持 Htt 在参与包含 HAP1、KIF5A 和动力蛋白的 mRNA 运输机制中的作用。
