Yates Darran M, Manser Catherine, De Vos Kurt J, Shaw Christopher E, McLoughlin Declan M, Miller Christopher C J
MRC Centre for Neurodegeneration Research, Department of Neuroscience P037, Institute of Psychiatry, King's College London, De Crespigny Park, Denmark Hill, London SE58AF, UK.
Eur J Cell Biol. 2009 Apr;88(4):193-202. doi: 10.1016/j.ejcb.2008.11.004. Epub 2009 Jan 14.
Neurofilaments are the intermediate filaments of neurons and are synthesised in neuronal cell bodies and then transported through axons. Neurofilament light chain (NFL) is a principal component of neurofilaments, and phosphorylation of NFL head domain is believed to regulate the assembly of neurofilaments. However, the role that NFL phosphorylation has on transport of neurofilaments is poorly understood. To address this issue, we monitored axonal transport of phosphorylation mutants of NFL. We mutated four known phosphorylation sites in NFL head domain to either preclude phosphorylation, or mimic permanent phosphorylation. Mutation to preclude phosphorylation had no effect on transport but mutation of three sites to mimic permanent phosphorylation inhibited transport. Mutation of all four sites together to mimic permanent phosphorylation proved especially potent at inhibiting transport and also disrupted neurofilament assembly. Our results suggest that NFL head domain phosphorylation is a regulator of neurofilament axonal transport.
神经丝是神经元的中间丝，在神经元细胞体中合成，然后通过轴突运输。神经丝轻链（NFL）是神经丝的主要成分，NFL头部结构域的磷酸化被认为可调节神经丝的组装。然而，NFL磷酸化对神经丝运输的作用却知之甚少。为了解决这个问题，我们监测了NFL磷酸化突变体的轴突运输。我们将NFL头部结构域中的四个已知磷酸化位点突变为要么阻止磷酸化，要么模拟永久磷酸化。阻止磷酸化的突变对运输没有影响，但三个位点突变为模拟永久磷酸化则抑制了运输。将所有四个位点一起突变为模拟永久磷酸化在抑制运输方面特别有效，并且还破坏了神经丝的组装。我们的结果表明，NFL头部结构域的磷酸化是神经丝轴突运输的调节剂。
