Kong J, Tung V W, Aghajanian J, Xu Z
Worcester Foundation for Biomedical Research, Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical Center, Shrewsbury, Massachusetts 01545, USA.
J Cell Biol. 1998 Mar 9;140(5):1167-76. doi: 10.1083/jcb.140.5.1167.
Dendrites play important roles in neuronal function. However, the cellular mechanism for the growth and maintenance of dendritic arborization is unclear. Neurofilaments (NFs), a major component of the neuronal cytoskeleton, are composed of three polypeptide subunits, NF-H, NF-M, and NF-L, and are abundant in large dendritic trees. By overexpressing each of the three NF subunits in transgenic mice, we altered subunit composition and found that increasing NF-H and/or NF-M inhibited dendritic arborization, whereas increasing NF-L alleviated this inhibition. Examination of cytoskeletal organization revealed that increasing NF-H and/or NF-M caused NF aggregation and dissociation of the NF network from the microtubule (MT) network. Increasing NF-H or NF-H together with NF-M further reduced NFs from dendrites. However, these changes were reversed by elevating the level of NF-L with either NF-H or NF-M. Thus, NF-L antagonizes NF-H and NF-M in organizing the NF network and maintaining a lower ratio of NF-H and NF-M to NF-L is critical for the growth of complex dendritic trees in motor neurons.
树突在神经元功能中发挥着重要作用。然而,树突分支生长和维持的细胞机制尚不清楚。神经丝(NFs)是神经元细胞骨架的主要成分,由三种多肽亚基NF-H、NF-M和NF-L组成,在大型树突中含量丰富。通过在转基因小鼠中过表达这三种NF亚基中的每一种,我们改变了亚基组成,发现增加NF-H和/或NF-M会抑制树突分支,而增加NF-L则可缓解这种抑制。对细胞骨架组织的检查显示,增加NF-H和/或NF-M会导致NF聚集以及NF网络与微管(MT)网络解离。增加NF-H或NF-H与NF-M一起会进一步减少树突中的NFs。然而,通过提高NF-L与NF-H或NF-M的水平,这些变化会被逆转。因此,在组织NF网络方面,NF-L拮抗NF-H和NF-M,并且维持较低的NF-H和NF-M与NF-L的比例对于运动神经元中复杂树突的生长至关重要。