Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons.
Posttranslational modifications of tubulin and the polarized transport of kinesin-1 in neurons.
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DOI：
10.1091/mbc.e09-01-0044
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发表时间：
2010-02-15
影响因子：
3.3
通讯作者：
Verhey KJ
中科院分区：
文献类型：
--
作者：
Hammond JW;Huang CF;Kaech S;Jacobson C;Banker G;Verhey KJ
在神经元极性发育过程中，驱动蛋白-1马达优先移位到轴突。我们发现，驱动蛋白-1的选择性不依赖于轴突和树突之间的差异，微管稳定性或微管蛋白乙酰化，但可能是指定的其他微管蛋白翻译后修饰。基于微管的马达的极化运输对于神经元的发育和功能至关重要。驱动蛋白-1运动域的选择性易位是已知最早的轴突身份标记，发生在形态分化之前。因此，驱动蛋白-1介导的运输可能有助于轴突规格。我们测试了微管蛋白的翻译后修饰是否影响驱动蛋白1马达在神经元发育过程中区分微管轨道的能力。我们检测到在极化阶段3海马神经元的轴突和小神经突之间的微管稳定性没有差异。相比之下，微管修饰富集在非极化阶段2细胞的神经突亚群和极化阶段3细胞的发育轴突中。这种富集与组成性激活的驱动蛋白-1马达的选择性积累相关。增加微管蛋白乙酰化，而不改变其他微管蛋白修饰的水平，没有改变极化细胞中驱动蛋白-1积累的选择性。然而，通过紫杉醇处理或抑制糖原合成酶激酶3β全面增强微管蛋白乙酰化、去酪氨酸化和多聚谷氨酰胺化，降低了驱动蛋白-1转位的选择性，并导致多个轴突的形成。尽管微管乙酰化增强了驱动蛋白-1的运动性，但在极化神经元细胞中驱动蛋白-1在轴突微管上的优先易位不是由单独的乙酰化决定的，而是可能由微管蛋白修饰的组合指定的。
During the development of neuronal polarity, the Kinesin-1 motor translocates preferentially to the axon. We show that Kinesin-1 selectivity does not depend on differences between axons and dendrites in microtubule stability or tubulin acetylation, but is likely specified by other tubulin posttranslational modifications. Polarized transport by microtubule-based motors is critical for neuronal development and function. Selective translocation of the Kinesin-1 motor domain is the earliest known marker of axonal identity, occurring before morphological differentiation. Thus, Kinesin-1–mediated transport may contribute to axonal specification. We tested whether posttranslational modifications of tubulin influence the ability of Kinesin-1 motors to distinguish microtubule tracks during neuronal development. We detected no difference in microtubule stability between axons and minor neurites in polarized stage 3 hippocampal neurons. In contrast, microtubule modifications were enriched in a subset of neurites in unpolarized stage 2 cells and the developing axon in polarized stage 3 cells. This enrichment correlated with the selective accumulation of constitutively active Kinesin-1 motors. Increasing tubulin acetylation, without altering the levels of other tubulin modifications, did not alter the selectivity of Kinesin-1 accumulation in polarized cells. However, globally enhancing tubulin acetylation, detyrosination, and polyglutamylation by Taxol treatment or inhibition of glycogen synthase kinase 3β decreased the selectivity of Kinesin-1 translocation and led to the formation of multiple axons. Although microtubule acetylation enhances the motility of Kinesin-1, the preferential translocation of Kinesin-1 on axonal microtubules in polarized neuronal cells is not determined by acetylation alone but is probably specified by a combination of tubulin modifications.
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影响因子：
64.8
作者：
Hubbert, C;Guardiola, A;Yao, TP
通讯作者：
Yao, TP
影响因子：
9.2
作者：
Dajas-Ballador, Federico;Jones, Emma V.;Whitmarsh, Alan J.
通讯作者：
Whitmarsh, Alan J.
影响因子：
16.2
作者：
Jacobson, C;Schnapp, B;Banker, GA
通讯作者：
Banker, GA
影响因子：
14.8
作者：
Kaech, Stefanie;Banker, Gary
通讯作者：
Banker, Gary
DOI：
10.1083/jcb.109.6.3085
发表时间：
1989-12
期刊：
The Journal of cell biology
影响因子：
--
作者：
Baas PW;Black MM;Banker GA
通讯作者：
Banker GA