Department of Genetics, University of Cambridge, Cambridge, United Kingdom.
Department of Cell Biology, University of Connecticut Health Center, Farmington, United States.
Elife. 2017 Jul 25;6:e23882. doi: 10.7554/eLife.23882.
Axons contain a smooth tubular endoplasmic reticulum (ER) network that is thought to be continuous with ER throughout the neuron; the mechanisms that form this axonal network are unknown. Mutations affecting reticulon or REEP proteins, with intramembrane hairpin domains that model ER membranes, cause an axon degenerative disease, hereditary spastic paraplegia (HSP). We show that axons have a dynamic axonal ER network, which these proteins help to model. Loss of HSP hairpin proteins causes ER sheet expansion, partial loss of ER from distal motor axons, and occasional discontinuities in axonal ER. Ultrastructural analysis reveals an extensive ER network in axons, which shows larger and fewer tubules in larvae that lack reticulon and REEP proteins, consistent with loss of membrane curvature. Therefore HSP hairpin-containing proteins are required for shaping and continuity of axonal ER, thus suggesting roles for ER modeling in axon maintenance and function.
轴突包含一个平滑的管状内质网 (ER) 网络，据认为该网络与神经元内的 ER 是连续的；形成这种轴突网络的机制尚不清楚。影响内质网蛋白或 REEP 蛋白的突变，其具有模拟 ER 膜的跨膜发夹结构域，会导致轴突退行性疾病遗传性痉挛性截瘫 (HSP)。我们表明轴突具有动态的轴突 ER 网络，这些蛋白质有助于对其进行建模。HSP 发夹蛋白的缺失会导致 ER 片层扩张、远端运动轴突中 ER 的部分丢失，以及偶尔出现轴突 ER 的不连续性。超微结构分析显示轴突中存在广泛的 ER 网络，在缺乏内质网蛋白和 REEP 蛋白的幼虫中，该网络显示出更大和更少的小管，这与膜曲率的丧失一致。因此，HSP 发夹蛋白对于轴突 ER 的形成和连续性是必需的，这表明 ER 建模在轴突维持和功能中发挥作用。
