The role for tubulin isotype diversity

微管蛋白同种型多样性的作用

• 批准号: BB/Y00485X/1
• 负责人: Julie Welburn
• 金额: $ 65.08万
• 依托单位: University of Edinburgh
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FY00485X%2F1
• 关键词: role; tubulin; isotype; diversity

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.

微管是存在于细胞质中执行基本任务的长的动态细丝。它们在细胞分裂过程中分离染色体，充当马达在细胞内运输货物的轨道，并有助于细胞的形状和结构。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，编码称为同种型的蛋白质变体。在本研究中，我们试图了解微管蛋白异源二聚体的组装是否是随机的（假设：9种α-微管蛋白同种型中的任何一种都可以与9种β-微管蛋白同种型中的任何一种组装），或者是否确定（假设：只有α-微管蛋白同种型的某些组合可以与特定的β-微管蛋白同种型组装）其次，我们将确定微管蛋白变体如何影响微管的组装以及与微管相互作用以构建轨道和细胞结构的蛋白质，并检查微管蛋白变体是否可以产生多种细胞结构。 第三，越来越多的患者被报道患有由特定微管蛋白基因的点突变引起的疾病。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、耳朵和鼻子感染。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，以便我们有一天可以帮助和缓解患者的症状。