TOG Proteins Are Spatially Regulated by Rac-GSK3β to Control Interphase Microtubule Dynamics.
TOG Proteins Are Spatially Regulated by Rac-GSK3β to Control Interphase Microtubule Dynamics.
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DOI：
10.1371/journal.pone.0138966
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Rogers SL
中科院分区：
文献类型：
--
作者：
Trogden KP;Rogers SL
微管由一组不同的蛋白质调节，这些蛋白质定位于微管加端（+TIP），在那里它们调节动态不稳定性并介导与细胞皮质、肌动蛋白丝和细胞器的相互作用。虽然个别+TIPs已被深入研究，我们了解他们的微管动力学的基本贡献，有越来越多的证据表明，这些蛋白质表现出串扰和可能的功能，共同整合微管行为和上游信号通路。在这项研究中，我们发现了果蝇中XMAP 215同源物Mini spindle（Msps）和CLASP同源物Orbit之间的一种新型蛋白质-蛋白质相互作用。这些蛋白质已被证明分别促进和抑制微管动力学。我们发现，微管动力学在细胞中通过Rac抑制外周板状体/板状体中的GSK 3 β而区域性地控制。GSK 3 β对Orbit的磷酸化触发Msps从微管正端到晶格的重新定位。Msps-Orbit结合位点的突变表明，这种相互作用是调节细胞外周微管动态不稳定性所必需的。基于我们的研究结果，我们提出Msps是一种新型的Rac效应器，与Orbit合作，区域调节微管动力学。
Microtubules are regulated by a diverse set of proteins that localize to microtubule plus ends (+TIPs) where they regulate dynamic instability and mediate interactions with the cell cortex, actin filaments, and organelles. Although individual +TIPs have been studied in depth and we understand their basic contributions to microtubule dynamics, there is a growing body of evidence that these proteins exhibit cross-talk and likely function to collectively integrate microtubule behavior and upstream signaling pathways. In this study, we have identified a novel protein-protein interaction between the XMAP215 homologue in Drosophila, Mini spindles (Msps), and the CLASP homologue, Orbit. These proteins have been shown to promote and suppress microtubule dynamics, respectively. We show that microtubule dynamics are regionally controlled in cells by Rac acting to suppress GSK3β in the peripheral lamellae/lamellipodium. Phosphorylation of Orbit by GSK3β triggers a relocalization of Msps from the microtubule plus end to the lattice. Mutation of the Msps-Orbit binding site revealed that this interaction is required for regulating microtubule dynamic instability in the cell periphery. Based on our findings, we propose that Msps is a novel Rac effector that acts, in partnership with Orbit, to regionally regulate microtubule dynamics.