Microtubule-associated protein 1B controls directionality of growth cone migration and axonal branching in regeneration of adult dorsal root ganglia neurons
Microtubule-associated protein 1B controls directionality of growth cone migration and axonal branching in regeneration of adult dorsal root ganglia neurons
复制标题
DOI：
10.1523/jneurosci.2254-04.2004
复制
发表时间：
2004-08-11
影响因子：
5.3
通讯作者：
Nothias, F
中科院分区：
文献类型：
--
作者：
Bouquet, C;Soares, S;Nothias, F
微管相关蛋白1B（microtubule-associated protein 1B，MAP 1B）是发育过程中最早表达的微管相关蛋白之一，主要定位于轴突和生长锥，在轴突生长中起重要作用。虽然在成人中普遍下调，我们已经表明，MAP 1B是组成性的高度表达在成人背根神经节（DRG），并与中央发芽和外周再生这些神经元。具有完整的MAP 1B无效等位基因的突变小鼠存活至成年期，表现出髓鞘直径和外周轴突传导速度的减小以及胼胝体的缺乏。在这里，为了确定MAP 1B在轴突再生中的功能，我们使用了来自该map 1b（-/-）小鼠系的成年DRG外植体和/或解离神经元的培养物。尽管缺乏MAP 1B的再生神经突的总长度与野生型对照相似，但我们的分析揭示了两个主要缺陷。首先，map 1b（-/-）神经突表现出显着（两倍）更高的终端和侧支。其次，生长锥的转动能力（即，正确方向的“选择”）受到损害。此外，缺乏MAP 1B可能会影响微管蛋白聚合物的翻译后修饰：定量分析显示生长锥内乙酰化微管的量减少，而酪氨酸化或去酪氨酸化微管的分布是正常的。已知生长锥转向和轴突分支形成都涉及微管网络的局部调节。我们的研究结果表明，MAP 1B在这些过程中发挥作用，在成人的塑料变化。特别是，这些数据表明MAP 1B的含义在局部协调组装的细胞骨架组件所需的分支和直的定向轴突生长。
During development, microtubule-associated protein 1B (MAP1B) is one of the earliest MAPs, preferentially localized in axons and growth cones, and plays a role in axonal outgrowth. Although generally downregulated in the adult, we have shown that MAP1B is constitutively highly expressed in adult dorsal root ganglia ( DRGs) and associated with central sprouting and peripheral regeneration of these neurons. Mutant mice with a complete MAP1B null allele that survive until adulthood exhibit a reduced myelin sheath diameter and conductance velocity of peripheral axons and lack of the corpus callosum. Here, to determine the function of MAP1B in axonal regeneration, we used cultures of adult DRG explants and/or dissociated neurons derived from this map1b(-/-) mouse line. Whereas the overall length of regenerating neurites lacking MAP1B was similar to wild-type controls, our analysis revealed two main defects. First, map1b(-/-) neurites exhibited significantly (twofold) higher terminal and collateral branching. Second, the turning capacity of growth cones (i.e., "choice" of a proper orientation) was impaired. In addition, lack of MAP1B may affect the post-translational modification of tubulin polymers: quantitative analysis showed a reduced amount of acetylated microtubules within growth cones, whereas the distribution of tyrosinated or detyrosinated microtubules was normal. Both growth cone turning and axonal branch formation are known to involve local regulation of the microtubule network. Our results demonstrate that MAP1B plays a role in these processes during plastic changes in the adult. In particular, the data suggest MAP1B implication in the locally coordinated assembly of cytoskeletal components required for branching and straight directional axon growth.