Neurofilaments and Neurofilament Proteins in Health and Disease.
Neurofilaments and Neurofilament Proteins in Health and Disease.
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DOI：
10.1101/cshperspect.a018309
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发表时间：
2017-04-03
影响因子：
7.2
通讯作者：
Nixon RA
中科院分区：
文献类型：
--
作者：
Yuan A;Rao MV;Veeranna;Nixon RA
神经丝（nf）是由四个亚基（NF-L[神经丝轻]；NF-M[神经丝中]；NF-H[神经丝重]和α-连接蛋白或外周蛋白）组成的异聚物，在组织特异性的中间丝（if）类别中是独一无二的，每个亚基都具有不同的结构域和功能。在这里，我们回顾了NFs如何为神经元的高度不对称几何结构提供结构支持，特别是为髓鞘轴突的显著径向扩张提供结构支持，髓鞘轴突对有效的神经传导速度至关重要。轴突中的NFs广泛地与细胞骨架的其他非if成分（包括微管、肌动蛋白丝和其他纤维细胞骨架元件）过桥并相互连接，以建立一个区域专门化的网络，该网络经历异常缓慢的局部周转，并作为组织其他细胞器和蛋白质的对接平台。我们还讨论了在轴突运输的缓慢阶段，一小群低聚体和短丝状前体是如何维持这个网络的。每个亚基上的磷酸化和去磷酸化事件的复杂模式调节着轴突细胞骨架内的丝组装、周转和组织。多种因素，尤其是周转率，决定了网络的大小，它可以沿着轴突变化很大。NF基因突变引起以亚基组装和NF聚集中断为特征的几种神经轴突疾病。其他NF改变与各种神经精神疾病有关。新的证据表明，NF亚基存在于突触后末端按钮中并影响神经传递，这表明NF蛋白可能有助于正常的突触功能和神经精神疾病状态。
Neurofilaments (NFs) are unique among tissue-specific classes of intermediate filaments (IFs) in being heteropolymers composed of four subunits (NF-L [neurofilament light]; NF-M [neurofilament middle];NF-H [neurofilament heavy];and α-internexin or peripherin), each having different domain structures and functions. Here, we review how NFs provide structural support for the highly asymmetric geometries of neurons and, especially, for the marked radial expansion of myelinated axons crucial for effective nerve conduction velocity. NFs in axons extensively cross-bridge and interconnect with other non-IF components of the cytoskeleton, including microtubules, actin filaments, and other fibrous cytoskeletal elements, to establish a regionally specialized network that undergoes exceptionally slow local turnover and serves as a docking platform to organize other organelles and proteins. We also discuss how a small pool of oligomeric and short filamentous precursors in the slow phase of axonal transport maintains this network. A complex pattern of phosphorylation and dephosphorylation events on each subunit modulates filament assembly, turnover, and organization within the axonal cytoskeleton. Multiple factors, and especially turnover rate, determine the size of the network, which can vary substantially along the axon. NF gene mutations cause several neuroaxonal disorders characterized by disrupted subunit assembly and NF aggregation. Additional NF alterations are associated with varied neuropsychiatric disorders. New evidence that subunits of NFs exist within postsynaptic terminal boutons and influence neurotransmission suggests how NF proteins might contribute to normal synaptic function and neuropsychiatric disease states.
神经丝蛋白在鱿鱼巨型轴突中磷酸化。
影响因子：
7.8
作者：
Pant, H C;Shecket, G;Gainer, H;Lasek, R J
通讯作者：
Lasek, R J
影响因子：
7.8
作者：
Schlaepfer, W W;Freeman, L A
通讯作者：
Freeman, L A