Yuasa-Kawada Junichi, Suzuki Ryoko, Kano Fumi, Ohkawara Takeshi, Murata Masayuki, Noda Masaharu
Division of Molecular Neurobiology, National Institute for Basic Biology, and Department of Molecular Biomechanics, The Graduate University for Advanced Studies, Okazaki, 444-8585, Japan.
Eur J Neurosci. 2003 Jun;17(11):2329-43. doi: 10.1046/j.1460-9568.2003.02664.x.
During development, cells undergo dynamic morphological changes by rearrangements of the cytoskeleton including microtubules. However, molecular mechanisms underlying the microtubule remodeling between orientated and disoriented formations are almost unknown. Here we found that novel subtypes of collapsin response mediator proteins (CRMP-As) and the originals (CRMP-Bs), which occur from the alternative usage of different first coding exons, are involved in this conversion of microtubule patterns. Overexpression of CRMP2A and CRMP2B in chick embryonic fibroblasts induced orientated and disoriented patterns of microtubules, respectively. Moreover, sequential overexpression of another subtype overcame the effect of the former expression of the countersubtype. Overexpression experiments in cultured chick retinae showed that CRMP2B promoted axon branching and suppressed axon elongation of ganglion cells, while CRMP2A blocked these effects when co-overexpressed. Our findings suggest that the opposing activities of CRMP2A and CRMP2B contribute to the cellular morphogenesis including neuronal axonogenesis through remodeling of microtubule organization.
在发育过程中，细胞通过包括微管在内的细胞骨架重排经历动态形态变化。然而，微管在定向和非定向形成之间重塑的分子机制几乎完全未知。在这里，我们发现了由不同的第一个编码外显子的交替使用产生的新型塌陷反应介导蛋白（CRMP - A）亚型和原始型（CRMP - B）参与了微管模式的这种转变。在鸡胚成纤维细胞中过表达CRMP2A和CRMP2B分别诱导了微管的定向和非定向模式。此外，另一种亚型的顺序过表达克服了前一种反义亚型表达的影响。在培养的鸡视网膜中的过表达实验表明，CRMP2B促进神经节细胞的轴突分支并抑制其轴突伸长，而当共过表达时CRMP2A阻断这些作用。我们的研究结果表明，CRMP2A和CRMP2B的相反活性通过微管组织重塑促进包括神经元轴突发生在内的细胞形态发生。
