PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule function in Caenorhabditis elegans neurons.
PTRN-1, a microtubule minus end-binding CAMSAP homolog, promotes microtubule function in Caenorhabditis elegans neurons.
复制标题
作者：
Richardson CE;Spilker KA;Cueva JG;Perrino J;Goodman MB;Shen K
在神经元过程中，微管（MT）提供结构支持，并作为分子马达的轨道。虽然已知神经元MT比非神经元细胞中的MT更稳定，但这种稳定性背后的分子机制尚未完全理解。在这项研究中，我们使用活荧光显微镜显示，C。线虫CAMSAP蛋白PTRN-1定位于沿着神经元突起的点，稳定MT灶，并促进MT在神经突中的聚合。电子显微镜显示，ptrn-1无效突变体有较少的MT和异常的MT组织中的PLM神经元。与MT解聚药物一起生长的动物在没有PTRN-1功能的情况下引起神经突分支的合成缺陷，表明PTRN-1促进MT稳定性。此外，ptrn-1无效突变体表现出异常的神经突形态和突触囊泡定位，这是部分依赖于dlk-1。我们的研究结果表明，PTRN-1代表了一个重要的机制，促进MT稳定的神经元。http://dx.doi.org/10.7554/eLife.01498.001微管是微小的管状结构，由称为微管蛋白的蛋白质的许多拷贝组成。微管在细胞内具有许多重要作用：它们是细胞骨架的一部分，为细胞提供结构支持;它们有助于在细胞分裂期间将染色体拉开;它们引导蛋白质和分子在细胞内的运输。大多数微管相对不稳定，根据细胞的需要进行连续的拆卸和重新组装。神经细胞分支中的微管是一个例外，随着时间的推移保持相对稳定。Richardson等人和Marcette等人已经表明，一种叫做PTRN-1的蛋白质在稳定蠕虫神经细胞中的微管方面具有重要作用。通过用荧光分子标记PTRN-1蛋白质，Richardson等人能够证明这些蛋白质沿着神经细胞内微管的长度存在。进一步的研究表明，PTRN-1蛋白稳定了这些神经细胞分支内的微管丝，并将它们固定在适当的位置。Richardson等人还发现，经过基因改造以阻止它们产生PTRN-1的蠕虫无法将某些分子运送到神经细胞之间的突触。此外，这些突变体也存在神经细胞分支的问题;然而，这些缺陷相对轻微，这表明其他分子和蛋白质与PTRN-1平行作用，以稳定神经细胞中的微管。进一步的工作应该能够识别这些因子，并阐明它们如何共同作用以稳定神经细胞中的微管。DOI：http://dx.doi.org/10.7554/eLife.01498.002网站
In neuronal processes, microtubules (MTs) provide structural support and serve as tracks for molecular motors. While it is known that neuronal MTs are more stable than MTs in non-neuronal cells, the molecular mechanisms underlying this stability are not fully understood. In this study, we used live fluorescence microscopy to show that the C. elegans CAMSAP protein PTRN-1 localizes to puncta along neuronal processes, stabilizes MT foci, and promotes MT polymerization in neurites. Electron microscopy revealed that ptrn-1 null mutants have fewer MTs and abnormal MT organization in the PLM neuron. Animals grown with a MT depolymerizing drug caused synthetic defects in neurite branching in the absence of ptrn-1 function, indicating that PTRN-1 promotes MT stability. Further, ptrn-1 null mutants exhibited aberrant neurite morphology and synaptic vesicle localization that is partially dependent on dlk-1. Our results suggest that PTRN-1 represents an important mechanism for promoting MT stability in neurons. DOI: http://dx.doi.org/10.7554/eLife.01498.001 Microtubules are tiny tubular structures made from many copies of proteins called tubulins. Microtubules have a number of important roles inside cells: they are part of the cytoskeleton that provides structural support for the cell; they help to pull chromosomes apart during cell division; and they guide the trafficking of proteins and molecules around inside the cell. Most microtubules are relatively unstable, undergoing continuous dis-assembly and re-assembly in response to the needs of the cell. The microtubules in the branches of nerve cells are an exception, remaining relatively stable over time. Now Richardson et al. and, independently, Marcette et al., have shown that a protein called PTRN-1 has an important role in stabilizing the microtubules in the nerve cells of nematode worms. By tagging the PTRN-1 proteins with fluorescent molecules, Richardson et al. were able to show that these proteins were present along the length of the microtubules within the nerve cells. Further work showed that the PTRN-1 proteins stabilize the microtubule filaments within the branches of these nerve cells and also hold them in position. Richardson et al. also found that worms that had been genetically modified to prevent them from producing PTRN-1 failed to traffic certain molecules to the synapses between nerve cells. Moreover, these mutants also had problems with the branching of their nerve cells; however, these defects were relatively mild, which suggests that other molecules and proteins act in parallel with PTRN-1 to stabilize microtubules in nerve cells. Further work should be able to identify these factors and elucidate how they work together to stabilize the microtubules in nerve cells. DOI: http://dx.doi.org/10.7554/eLife.01498.002