Atlastin-1 调节树突内质网的形态和功能。
Atlastin-1 regulates morphology and function of endoplasmic reticulum in dendrites.
机构信息
National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Datun Road, Chaoyang District, Beijing, 100101, China.
University of Chinese Academy of Sciences, Beijing, 100101, China.
出版信息
Nat Commun. 2019 Feb 4;10(1):568. doi: 10.1038/s41467-019-08478-6.
Endoplasmic reticulum (ER) is characterized by interconnected tubules and sheets. Neuronal ER adopts specific morphology in axons, dendrites and soma. Here we study mechanisms underlying ER morphogenesis in a C. elegans sensory neuron PVD. In PVD soma and dendrite branch points, ER tubules connect to form networks. ER tubules fill primary dendrites but only extend to some but not all dendritic branches. We find that the Atlastin-1 ortholog, atln-1 is required for neuronal ER morphology. In atln-1 mutants with impaired GTPase activity, ER networks in soma and dendrite branch points are reduced and replaced by tubules, and ER tubules retracted from high-order dendritic branches, causing destabilized microtubule in these branches. The abnormal ER morphology likely causes defects in mitochondria fission at dendritic branch points. Mutant alleles of Atlastin-1 found in Hereditary Spastic Paraplegia (HSP) patients show similar ER phenotypes, suggesting that neuronal ER impairment contributes to HSP disease pathogenesis.
内质网（ER）的特征是相互连接的小管和薄片。神经元 ER 在轴突、树突和胞体中采用特定的形态。在这里，我们研究秀丽隐杆线虫感觉神经元 PVD 中 ER 形态发生的机制。在 PVD 胞体和树突分支点，ER 小管连接形成网络。ER 小管填充初级树突，但仅延伸到一些而不是所有的树突分支。我们发现，Atlastin-1 同源物 atln-1 是神经元 ER 形态所必需的。在 GTPase 活性受损的 atln-1 突变体中，胞体和树突分支点的 ER 网络减少，被小管取代，并且 ER 小管从高级树突分支回缩，导致这些分支中的微管不稳定。异常的 ER 形态可能导致树突分支点线粒体分裂缺陷。在遗传性痉挛性截瘫（HSP）患者中发现的 Atlastin-1 突变等位基因表现出类似的 ER 表型，表明神经元 ER 损伤导致 HSP 疾病发病机制。
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