Jentzsch Jana, Wunderlich Hannes, Thein Marinus, Bechthold Julia, Brehm Lucas, Krauss Sebastian W, Weiss Matthias, Ersfeld Klaus
Molecular Parasitology, Department of Biology, University of Bayreuth, Universitätsstraße 30, 95447 Bayreuth, Germany.
Experimental Physics I, Department of Physics, University of Bayreuth, Universitätsstraße 30, 95447 Bayreuth, Germany.
J Cell Sci. 2024 Feb 1;137(3). doi: 10.1242/jcs.261740. Epub 2024 Feb 12.
Tubulin polyglutamylation, catalysed by members of the tubulin tyrosine ligase-like (TTLL) protein family, is an evolutionarily highly conserved mechanism involved in the regulation of microtubule dynamics and function in eukaryotes. In the protozoan parasite Trypanosoma brucei, the microtubule cytoskeleton is essential for cell motility and maintaining cell shape. In a previous study, we showed that T. brucei TTLL6A and TTLL12B are required to regulate microtubule dynamics at the posterior cell pole. Here, using gene deletion, we show that the polyglutamylase TTLL1 is essential for the integrity of the highly organised microtubule structure at the cell pole, with a phenotype distinct from that observed in TTLL6A- and TTLL12B-depleted cells. Reduced polyglutamylation in TTLL1-deficient cells also leads to increased levels in tubulin tyrosination, providing new evidence for an interplay between the tubulin tyrosination and detyrosination cycle and polyglutamylation. We also show that TTLL1 acts differentially on specific microtubule doublets of the flagellar axoneme, although the absence of TTLL1 appears to have no measurable effect on cell motility.
微管蛋白多聚谷氨酰胺化由微管蛋白酪氨酸连接酶样（TTLL）蛋白家族成员催化，是一种在进化上高度保守的机制，参与真核生物中微管动力学和功能的调节。在原生动物寄生虫布氏锥虫中，微管细胞骨架对于细胞运动和维持细胞形态至关重要。在先前的一项研究中，我们表明布氏锥虫TTLL6A和TTLL12B是调节细胞后极微管动力学所必需的。在这里，通过基因缺失，我们表明多聚谷氨酰胺酶TTLL1对于细胞极高度组织化的微管结构的完整性至关重要，其表型与在TTLL6A和TTLL12B缺失细胞中观察到的不同。TTLL1缺陷细胞中多聚谷氨酰胺化的减少也导致微管蛋白酪氨酸化水平升高，为微管蛋白酪氨酸化和去酪氨酸化循环与多聚谷氨酰胺化之间的相互作用提供了新证据。我们还表明，TTLL1对鞭毛轴丝的特定微管双联体有不同的作用，尽管TTLL1的缺失似乎对细胞运动没有可测量的影响。
