The role for tubulin isotype diversity

微管是存在于细胞细胞质中执行基本任务的长而动态的细丝。它们在细胞分裂过程中分离染色体，充当马达的轨道，在细胞中运输货物，并对细胞的形状和结构起作用。微管由α / β微管蛋白异二聚体组装而成。人类有9个α -微管蛋白和β -微管蛋白基因，它们编码被称为同型的蛋白质变体。在这项资助中，我们试图了解微管蛋白异二聚体的组装是随机的（假设：9种α -微管蛋白同型中的任何一种都可以与9种β -微管蛋白同型中的任何一种组装），还是确定的（假设：只有某些α -微管蛋白同型的组合可以与特定的β -微管蛋白同型组装）。其次，我们将确定微管蛋白变异如何影响微管的组装以及与微管相互作用以建立轨道和细胞结构的蛋白质，并检查微管蛋白变异是否可以产生各种细胞结构。第三，据报道，越来越多的患者患有由特定微管蛋白基因点突变引起的疾病。最近，我们在世界范围内首次发现了原发性纤毛运动障碍患者，他们的微管蛋白基因发生了突变。这种疾病会导致肺部粘液积聚和气道炎症，并导致肺部、耳部和鼻部感染。在这些患者中，纤毛中的微管缺失。我们的最后一个目标是了解这些微管蛋白突变是如何导致PCD疾病的，这样我们就可以有一天帮助和缓解患者的症状。

Microtubules are long dynamic filaments present in the cytoplasm of cells that perform essential tasks. They separate chromosomes during cell division, act as tracks for motors to transport cargos across the cell and contribute to cell shape and architecture. Microtubules are assembled from alpha/beta-tubulin heterodimers. There are 9 alpha-tubulin and beta-tubulin genes in humans, that code for protein variants called isotypes. In this grant, we seek to understand whether tubulin heterodimer assembly is random (hypothesis: any of the 9 alpha-tubulin isotypes can assemble with any of the 9 beta-tubulin isotypes), or whether it is determined (hypothesis: only certain combinations of alpha-tubulin isotypes can assemble with specific beta-tubulin isotypes).Second we will determine how the tubulin variants affect the assembly of microtubules and the proteins that interact with microtubules to build tracks and cellular structures, and examine if tubulin variants can generate a variety of cellular structures. Third, a growing number of patients are reported to have diseases caused by point mutations to specific tubulin genes. Very recently for the first time worldwide, we have identified patients with Primary Ciliary Dyskinesia, which have mutations in their tubulin genes. This disease causes mucus build-up in the lungs and inflammation of airways, with infections in the lungs, ear and nose. In these patients, the microtubules in the cilia are absent. Our last aim is to understand how these tubulin mutations cause the PCD disease, so that we can one day help and relieve patients' symptoms.