Department of Anatomy and Division of Brain Korea 21 Biomedical Science, College of Medicine, Korea University, 126-1, 5-Ka, Anam-Dong, Seongbuk-Gu, Seoul 136-705, Republic of Korea.
Biochem Biophys Res Commun. 2012 Jun 1;422(2):250-5. doi: 10.1016/j.bbrc.2012.04.136. Epub 2012 Apr 30.
Tamalin is a scaffold protein known to regulate membrane trafficking through its interaction with cytohesin-2/ARNO, guanine nucleotide exchange factor (GEF) on ADP-ribosylation factor (Arf) 1/6, and induces actin reorganization. However, the neuronal function of Tamalin is not well understood. Here, we report that Tamalin participates in neurite development through the association with exchange factor for Arf6 (EFA6A)/Arf6 signaling. In immature hippocampal neuron, Tamalin knockdown markedly reduced the dendritic outgrowth, the number of dendritic tips and the levels of filamentous actin (F-actin) and microtubule-associated protein 2 (MAP2) in dendrites. In addition, Tamalin colocalized with EFA6A and Arf6 in the dendritic shaft. Tamalin knockdown reduced the number, size, and intensity of endogenous EFA6A cluster, whereas overexpression of Tamalin showed opposite effects compared with those of knockdown. These results suggest that Tamalin is responsible for neuronal dendritic development via regulation of EFA6A/Arf6-mediated cytoskeleton dynamics.
塔马林是一种支架蛋白，已知通过与细胞骨架蛋白 2/ARNO、ADP-核糖基化因子 1/6（Arf）上的鸟嘌呤核苷酸交换因子（GEF）的相互作用，调节膜运输，并诱导肌动蛋白重组。然而，塔马林在神经元中的功能尚未完全了解。在这里，我们报告说，塔马林通过与 Arf6 交换因子（EFA6A）/Arf6 信号转导相关联，参与神经突发育。在未成熟的海马神经元中，塔马林敲低显著减少树突的生长、树突棘的数量以及树突中丝状肌动蛋白（F-actin）和微管相关蛋白 2（MAP2）的水平。此外，塔马林与 EFA6A 和 Arf6 在树突干中共定位。塔马林敲低减少了内源性 EFA6A 簇的数量、大小和强度，而塔马林的过表达与敲低相比表现出相反的效果。这些结果表明，塔马林通过调节 EFA6A/Arf6 介导的细胞骨架动力学，负责神经元树突发育。
