Studies on regulation of structure and function of primary cilia by tubulin polyglutamylation

在这项研究中，我们旨在确定在初级纤毛中调节微管蛋白多谷氨酰化的酶。我们最终确定了三种酶，TTLL1， TTLL6和CCP1，作为初级纤毛中的多谷氨酰化调节酶。我们发现，通过阻断TTLL6在初级纤毛中的定位或直接抑制TTLL6的功能，微管蛋白多谷氨酰化对于维持纤毛轴突的结构完整性至关重要。结果表明微管蛋白多谷氨酰化失调与纤毛疾病Joubert综合征有关。我们还证明了适当的多谷氨酰化水平对视网膜感光细胞的维持是必不可少的。此外，我们发现，在ccp1缺陷小鼠视网膜中，光感受器细胞中一种蛋白质的细胞内分布受到失调的超多谷氨酰化的影响。

In this study, we aimed to identify enzymes that regulated tubulin polyglutamylation in primary cilia. We have finally identified three enzymes, TTLL1, TTLL6, and CCP1, as polyglutamylation-regulating enzymes in primary cilia. We found, by blocking the localization of TTLL6 into primary cilia or by the direct inhibition of TTLL6 function, that tubulin polyglutamylation was essential for maintaining the structural integrity of the ciliary axonemes. The results suggest an association of the dysregulation of tubulin polyglutamylation with a ciliary disease, Joubert syndrome. We also demonstrated that appropriate polyglutamylation level was essential for the maintenance of retinal photoreceptor cells. In addition, we found that intracellular distribution of a protein in photoreceptor cells were affected by the dysregulated hyper-polyglutamylation in CCP1-deficient mouse retina.