Compartmentalized Calcium Signaling in Cilia Regulates Intraflagellar Transport
Compartmentalized Calcium Signaling in Cilia Regulates Intraflagellar Transport
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DOI：
10.1016/j.cub.2013.09.059
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发表时间：
2013-11-18
期刊：
影响因子：
9.2
通讯作者：
Wheeler, Glen L.
中科院分区：
文献类型：
--
作者：
Collingridge, Peter;Brownlee, Colin;Wheeler, Glen L.
鞭毛内运输 (IFT) 是纤毛和鞭毛在信号传导和运动中许多重要细胞作用的基础 [1-4]。微管马达驱动蛋白 2 和细胞质动力蛋白 1b 沿着轴丝驱动 IFT 颗粒（携带纤毛成分蛋白的蛋白质复合物），以促进纤毛的组装和维护。 IFT 主要由 IFT 颗粒上装载的货物来调节，尽管有证据表明 IFT 颗粒也表现出不同的运动速率 [5-7]。在这里，我们证明鞭毛内 Ca2+ 升高可以直接调节 IFT 颗粒的运动。在模型藻类衣藻中，IFT 驱动的粘附鞭毛膜糖蛋白的运动能够实现鞭毛介导的滑动运动 [8-10]。我们发现表面接触促进了衣藻鞭毛中 IFT 颗粒的局部积累。高度区室化的鞭毛内 Ca2+ 升高启动暂停的 IFT 颗粒的逆行运输以调节其积累。滑动运动仅在尾随（拖动）鞭毛中诱导机械敏感的鞭毛内 Ca2+ 升高，从而专门清除单个鞭毛中积累的微管马达并防止徒劳的拔河。我们的结果表明，区室化的纤毛内 Ca2+ 信号传导可以调节 IFT 颗粒的运动，因此可能在指导许多纤毛蛋白的运动和分布中发挥核心作用。
Intraflagellar transport (IFT) underpins many of the important cellular roles of cilia and flagella in signaling and motility [1-4]. The microtubule motors kinesin-2 and cytoplasmic dynein 1b drive IFT particles (protein complexes carrying ciliary component proteins) along the axoneme to facilitate the assembly and maintenance of cilia. IFT is regulated primarily by cargo loading onto the IFT particles, although evidence suggests that IFT particles also exhibit differential rates of movement [5-7]. Here we demonstrate that intraflagellar Ca2+ elevations act to directly regulate the movement of IFT particles. IFT-driven movement of adherent flagella membrane glycoproteins in the model alga Chlamydomonas enables flagella-mediated gliding motility [8-10]. We find that surface contact promotes the localized accumulation of IFT particles in Chlamydomonas flagella. Highly compartmentalized intraflagellar Ca2+ elevations initiate retrograde transport of paused IFT particles to modulate their accumulation. Gliding motility induces mechanosensitive intraflagellar Ca2+ elevations in trailing (dragging) flagella only, acting to specifically clear the accumulated microtubule motors from individual flagella and prevent a futile tug-of-war. Our results demonstrate that compartmentalized intraciliary Ca2+ signaling can regulate the movement of IFT particles and is therefore likely to play a central role in directing the movement and distribution of many ciliary proteins.