PULL AND PUSH IN NEURITE ELONGATION - OBSERVATIONS ON THE EFFECTS OF DIFFERENT CONCENTRATIONS OF CYTOCHALASIN-B AND TAXOL
PULL AND PUSH IN NEURITE ELONGATION - OBSERVATIONS ON THE EFFECTS OF DIFFERENT CONCENTRATIONS OF CYTOCHALASIN-B AND TAXOL
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DOI：
10.1002/cm.970080302
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发表时间：
1987-01-01
影响因子：
--
通讯作者：
RESSLER, AH
中科院分区：
文献类型：
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作者：
LETOURNEAU, PC;SHATTUCK, TA;RESSLER, AH
神经突伸长涉及两种不同的细胞骨架功能，即细胞骨架和相关细胞器向神经突尖端的顺行运输的“推”，以及生长锥中突起和张力产生所施加的“拉”。我们通过药物toxol和细胞松弛素B（CB）研究了这两种活性在轴突伸长中的作用，它们分别作用于关键的细胞骨架成分微管和肌动蛋白丝。当用浓度低于0.2 μ g/ml的CB处理神经元时，神经突伸长、生长锥突出和神经突张力都以类似的浓度依赖性方式被抑制。在CB浓度高于0.3 μ g/ml时不存在突出活性和张力，而神经突延伸继续处于平台水平。因此，“牵拉”确实调节，但它不是神经突伸长所必需的。令人惊讶的是，紫杉醇对神经突伸长的抑制作用被CB的加入所消除，CB的加入水平基本上破坏了神经突的肌动蛋白丝。由紫杉醇-CB神经元延伸的神经突是不分支的，并且奇怪地不附着于基底层。当CB加入到紫杉醇处理的神经元中时，即使蛋白质合成严重减少，神经突也会迅速延伸。我们建议，紫杉醇抑制微管运输的神经突，这种抑制的“推”是逆转的CB对细胞质基质的破坏性影响，使紫杉醇诱导的微管束被远端运输。
Neurite elongation involves two distinct cytoskeletal functions the "push" of anterograde transport of the cytoskeleton and associated organelles to the neurite tip, and the "pull" exerted by protrusion and generation of tensions in the growth cone. We investigated the roles of these two activities in neurite elongation via the drugs toxol and cytochalasin B (CB), which act on the key cytoskeletal components, microtubules and actin filaments, respectively. When neurons are treated with concentrations of CB below 0.2 .mu.g/ml, neurite elongation, growth cone protrusion, and neurite tension are all inhibited in a similar concentration dependent manner. Protrusive activity and tensions are absent at CB concentrations above 0.3 .mu.g/ml, yet neurite elongation continues at a plateau level. Thus, "pull" does modulate, but it is not required for neurite elongation. Surprisingly, the inhibitory effects of taxol on neurite elongation are removed by the addition of CB at levels that substantially disrupt the actin filaments of neurites. The neurites extended by taxol-CB neurons are unbranched and curiously unattached to the substratum. When CB is added to taxol-treated neurons, neurite extension begins rapidly, even if protein synthesis is severely reduced. We propose that taxol inhibits microtubule transport in neurites, and this inhibition of "push" is reversed by the disruptive effects of CB on the cytoplasmic matrix, allowing taxol-induced microtubule bundles to be transported distally.