Tubulin Polyglutamylation Regulates Axonemal Motility by Modulating Activities of Inner-Arm Dyneins
Tubulin Polyglutamylation Regulates Axonemal Motility by Modulating Activities of Inner-Arm Dyneins
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DOI：
10.1016/j.cub.2009.12.058
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发表时间：
2010-03-09
期刊：
影响因子：
9.2
通讯作者：
Kamiya, Ritsu
中科院分区：
文献类型：
--
作者：
Kubo, Tomohiro;Yanagisawa, Haru-aki;Kamiya, Ritsu
微管蛋白多谷氨酰化是在α-微管蛋白和β-微管蛋白[1，2]的C末端的谷氨酸残基的伽马-羧基上添加多个谷氨酸的修饰。这种修饰与轴突运输和纤毛运动的调节有关。然而，它在纤毛中的分子功能仍不清楚。在这里，使用一个新的莱茵衣藻突变体(Tpg1)，它缺乏人类TTLL9，一种谷氨酸连接酶[3]的同源物，我们发现α-微管蛋白中缺乏长的多谷氨酸侧链，适度地削弱了鞭毛的运动性，而不明显损害轴丝结构。此外，tpg1和oda2的双重突变导致外臂动力蛋白丢失，完全缺乏运动性。更令人惊讶的是，当用蛋白酶和ATIP处理时，这个瘫痪的双突变体的轴丝显示出比运动型oda2轴丝更快的微管滑动。这些和其他结果表明，多谷氨酰化主要通过调节臂内动力蛋白的功能来直接调节微管-动力蛋白的相互作用。
Tubulin polyglutamylation is a modification that adds multiple glutamates to the gamma-carboxyl group of a glutamate residue in the C-terminal tails of alpha- and beta-tubulin [1, 2]. This modification has been implicated in the regulation of axonal transport and ciliary motility. However, its molecular function in cilia remains unknown. Here, using a novel Chlamydomonas reinhardtii mutant (tpg1) that lacks a homolog of human TTLL9, a glutamic acid ligase enzyme [3], we found that the lack of a long polyglutamate side chain in alpha-tubulin moderately weakens flagellar motility without noticeably impairing the axonemal structure. Furthermore, the double mutant of tpg1 with oda2, a mutation that leads to loss of outer-arm dynein, completely lacks motility. More surprisingly, when treated with protease and ATIP, the axoneme of this paralyzed double mutant displayed faster microtubule sliding than the motile oda2 axoneme. These and other results suggest that polyglutamylation directly regulates microtubule-dynein interaction mainly by modulating the function of inner-arm dyneins.