Structures and interactions in 'bottlebrush' neurofilaments: the role of charged disordered proteins in forming hydrogel networks
Structures and interactions in 'bottlebrush' neurofilaments: the role of charged disordered proteins in forming hydrogel networks
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DOI：
10.1042/bst20120101
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发表时间：
2012-10-01
影响因子：
3.9
通讯作者：
Safinya, Cyrus R.
中科院分区：
文献类型：
--
作者：
Beck, Roy;Deek, Joanna;Safinya, Cyrus R.
神经丝是脊椎动物有髓轴突的主要细胞骨架成分，由三种不同分子量的亚基蛋白NF-L（低）、NF-M（中）和NF-H（高）组成，它们组装形成具有突出的内在无序C-末端侧臂的成熟丝。侧臂介导的NF组装体的液晶凝胶网络在神经元过程的机械稳定性中起关键作用。由于NF过度积累或不正确的侧臂相互作用导致的NF网络的破坏是包括肌萎缩侧索硬化症在内的运动神经元疾病的标志。使用同步辐射小角X射线散射和各种显微镜技术，我们已经调查的亚基侧臂上的结构和相互作用的NF的肽电荷的作用。我们的研究结果，这描绘了不同的作用，NF-M和NF-H在调节NF的相互作用，揭示了可能的机制中断的最佳机械网络性能。
NFs (neurofilaments), the major cytoskeletal constituent of myelinated axons in vertebrates, consist of three different molecular-mass subunit proteins, NF-L (low), NF-M (medium) and NF-H (high), assembled to form mature filaments with protruding intrinsically disordered C-terminal side-arms. Liquid crystal gel networks of side-arm-mediated NF assemblies play a key role in the mechanical stability of neuronal processes. Disruptions of the NF network, due to NF overaccumulation or incorrect side-arm interactions, are a hallmark of motor neuron diseases including amyotrophic lateral sclerosis. Using synchrotron small-angle X-ray scattering and various microscopy techniques, we have investigated the role of the peptide charges in the subunit side-arms on the structure and interaction of NFs. Our findings, which delineate the distinct roles of NF-M and NF-H in regulating NF interactions, shed light on possible mechanisms of disruption of optimal mechanical network properties.