Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin.
Antagonistic Functions of MBP and CNP Establish Cytosolic Channels in CNS Myelin.
复制标题
MBP和CNP的拮抗功能在CNS髓鞘中建立胞质通道。
DOI：
10.1016/j.celrep.2016.12.053
复制
发表时间：
2017-01-10
期刊：
影响因子：
8.8
通讯作者：
Simons M
中科院分区：
文献类型：
--
作者：
Snaidero N;Velte C;Myllykoski M;Raasakka A;Ignatev A;Werner HB;Erwig MS;Möbius W;Kursula P;Nave KA;Simons M
髓鞘是高度特化的神经胶质细胞沿沿着轴突以规则间隔的节段铺设的多层质膜延伸。最近的研究表明，髓鞘是代谢活跃，并能够与下面的轴突。为了在功能上连接到神经元，少突胶质细胞维持非致密髓鞘作为细胞质纳米通道。在这里，我们使用高压冷冻的电子显微镜研究这些细胞质区域内的髓鞘接近其天然状态。我们鉴定了2，′3′-环核苷酸3′-磷酸二酯酶（CNP），一种以前参与维持轴突完整性的少突胶质细胞特异性蛋白，作为髓磷脂隔室中产生和维持细胞质的重要因素。我们提供的证据表明，CNP直接关联和组织肌动蛋白细胞骨架，从而提供了一个细胞内的支柱，抵消髓鞘碱性蛋白（MBP）的膜压实。我们的研究提供了一个分子和结构框架，了解髓鞘如何维持其细胞质作为一个活跃的轴突胶质细胞单位的功能。髓鞘中接近其天然状态的“细胞质通道”的表征MBP和CNP在产生细胞质通道中的拮抗功能CNP与肌动蛋白相互作用并使肌动蛋白成束降低MBP水平挽救了CNP缺陷小鼠的轴突病变Snaidero et al.提供证据表明，通过MBP和CNP的拮抗剂功能，在髓鞘中产生了富含细胞质的通道系统。作者认为，这些通道需要提供营养支持神经元和维持功能轴突胶质细胞单位在很长一段时间。
The myelin sheath is a multilamellar plasma membrane extension of highly specialized glial cells laid down in regularly spaced segments along axons. Recent studies indicate that myelin is metabolically active and capable of communicating with the underlying axon. To be functionally connected to the neuron, oligodendrocytes maintain non-compacted myelin as cytoplasmic nanochannels. Here, we used high-pressure freezing for electron microscopy to study these cytoplasmic regions within myelin close to their native state. We identified 2,′3′-cyclic nucleotide 3′-phosphodiesterase (CNP), an oligodendrocyte-specific protein previously implicated in the maintenance of axonal integrity, as an essential factor in generating and maintaining cytoplasm within the myelin compartment. We provide evidence that CNP directly associates with and organizes the actin cytoskeleton, thereby providing an intracellular strut that counteracts membrane compaction by myelin basic protein (MBP). Our study provides a molecular and structural framework for understanding how myelin maintains its cytoplasm to function as an active axon-glial unit. Characterization of “cytoplasmic channels” in myelin close to their native state Antagonistic functions of MBP and CNP in generating cytoplasmic channels CNP interacts with and bundles actin Reducing MBP levels rescues axonal pathology in CNP-deficient mice Snaidero et al. provide evidence that a system of cytoplasmic-rich channels is generated in myelin sheaths by the antagonist function of MBP and CNP. The authors suggest that these channels are required to provide trophic support to neurons and maintain functional axon-glial units over a long period of time.