MRC Laboratory for Molecular Cell Biology, University College London, London, WC1E 6BT, UK.
J Cell Sci. 2010 Aug 15;123(Pt 16):2708-16. doi: 10.1242/jcs.068726. Epub 2010 Jul 20.
Microtubule dynamics are dominated by events at microtubule plus ends as they switch between discrete phases of growth and shrinkage. Through their ability to generate force and direct polar cell transport, microtubules help to organise global cell shape and polarity. Conversely, because plus-end binding proteins render the dynamic instability of individual microtubules sensitive to the local intracellular environment, cyto-architecture also affects the overall distribution of microtubules. Despite the importance of plus-end regulation for understanding microtubule cytoskeletal organisation and dynamics, little is known about the signalling mechanisms that trigger changes in their behaviour in space and time. Here, we identify a microtubule-associated kinase, Drosophila Tao-1, as an important regulator of microtubule stability, plus-end dynamics and cell shape. Active Tao-1 kinase leads to the destabilisation of microtubules. Conversely, when Tao-1 function is compromised, rates of cortical-induced microtubule catastrophe are reduced and microtubules contacting the actin cortex continue to elongate, leading to the formation of long microtubule-based protrusions. These data reveal a role for Tao-1 in controlling the dynamic interplay between microtubule plus ends and the actin cortex in the regulation of cell form.
微管动力学主要由微管正极端的事件主导,因为它们在生长和收缩的离散阶段之间切换。通过产生力和指导极性细胞运输的能力,微管有助于组织全局细胞形状和极性。相反,由于正端结合蛋白使单个微管的动态不稳定性对局部细胞内环境敏感,细胞结构也会影响微管的整体分布。尽管正端调节对于理解微管细胞骨架的组织和动力学非常重要,但对于触发其在空间和时间上行为变化的信号机制知之甚少。在这里,我们确定了一种微管相关激酶,果蝇 Tao-1,作为微管稳定性、正端动力学和细胞形状的重要调节剂。活性 Tao-1 激酶导致微管不稳定。相反,当 Tao-1 功能受损时,皮质诱导的微管崩溃的速度降低,并且与肌动蛋白皮质接触的微管继续伸长,导致基于微管的长突起的形成。这些数据揭示了 Tao-1 在控制微管正极端和肌动蛋白皮质之间的动态相互作用,以调节细胞形态中的作用。