Department of Molecular Neurogenetics, Center for Molecular Neurobiology, ZMNH, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
PLoS One. 2013 Sep 24;8(9):e75603. doi: 10.1371/journal.pone.0075603. eCollection 2013.
Kinesin superfamily proteins (KIFs) are molecular motors that transport cellular cargo along the microtubule cytoskeleton. KIF21B is a neuronal kinesin that is highly enriched in dendrites. The regulation and specificity of microtubule transport involves the binding of motors to individual cargo adapters and accessory proteins. Moreover, posttranslational modifications of either the motor protein, their cargos or tubulin regulate motility, cargo recognition and the binding or unloading of cargos. Here we show that the ubiquitin E3 ligase TRIM3, also known as BERP, interacts with KIF21B via its RBCC domain. TRIM3 is found at intracellular and Golgi-derived vesicles and co-localizes with the KIF21B motor in neurons. Trim3 gene deletion in mice and TRIM3 overexpression in cultured neurons both suggested that the E3-ligase function of TRIM3 is not involved in KIF21B degradation, however TRIM3 depletion reduces the motility of the motor. Together, our data suggest that TRIM3 is a regulator in the modulation of KIF21B motor function.
驱动蛋白超家族蛋白（KIFs）是沿着微管细胞骨架运输细胞货物的分子马达。KIF21B 是一种富含树突的神经元驱动蛋白。微管运输的调节和特异性涉及到马达与单个货物衔接器和辅助蛋白的结合。此外，马达蛋白、其货物或微管的翻译后修饰调节运动、货物识别以及货物的结合或卸载。在这里，我们表明泛素 E3 连接酶 TRIM3（也称为 BERP）通过其 RBCC 结构域与 KIF21B 相互作用。TRIM3 存在于细胞内和高尔基体衍生的小泡中，并与神经元中的 KIF21B 马达共定位。在小鼠中敲除 Trim3 基因和在培养的神经元中过表达 TRIM3 都表明，TRIM3 的 E3 连接酶功能不参与 KIF21B 的降解，然而 TRIM3 的耗竭会降低马达的运动性。总之，我们的数据表明，TRIM3 是调节 KIF21B 马达功能的调节剂。
