Rab6 regulation of the kinesin family KIF1C motor domain contributes to Golgi tethering.
Rab6 regulation of the kinesin family KIF1C motor domain contributes to Golgi tethering.
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DOI：
10.7554/elife.06029
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发表时间：
2015-03-30
期刊：
影响因子：
7.7
通讯作者：
Pfeffer SR
中科院分区：
文献类型：
--
作者：
Lee PL;Ohlson MB;Pfeffer SR
大多数驱动蛋白将货物结合在其C末端，并利用N末端的运动结构域沿微管移动。我们在此报道KIF1C的一种新功能：它运输Rab6A囊泡，并能影响高尔基体的组织结构。这些活性与KIF1C通过其运动结构域和C末端直接结合高尔基体蛋白Rab6A的能力相关。Rab6A与运动结构域的结合在体外和细胞内抑制微管相互作用，减少了可移动的KIF1C的量。KIF1C的缺失减缓了蛋白质向细胞表面的运输，干扰了囊泡的运动，并引发高尔基体碎片化。在缺乏完整微管网络的细胞中，KIF1C能够保护高尔基体膜免于碎片化。修复碎片化需要使KIF1C能够在两端结合Rab6A的序列，但不需要KIF1C的运动功能。Rab6A与KIF1C运动结构域的结合代表了一种对驱动蛋白运动的全新调节模式，可能对KIF1C的细胞功能具有重要影响。
DOI: http://dx.doi.org/10.7554/eLife.06029.001
在我们的细胞内有许多发挥重要作用的区室。被称为囊泡的小泡状包裹在这些区室之间运输蛋白质和其他分子。这些囊泡可由一类被称为驱动蛋白的运动蛋白在细胞内运输，驱动蛋白沿着一种被称为微管的丝状网络移动。
驱动蛋白有两个部分，被称为N末端和C末端。在大多数情况下，N末端包含与微管结合并沿其移动的运动结构域，而C末端与囊泡或其他细胞区室结合。附着在区室上的是另一类被称为Rab GTP酶的蛋白质家族成员。这些蛋白质帮助驱动蛋白与区室结合，但尚不清楚这些蛋白质是否或如何控制驱动蛋白的活性。
在此，Lee等人研究了一种被称为KIF1C的驱动蛋白。实验表明，这种驱动蛋白能够沿着微管运输含有一种被称为Rab6A的Rab - GTP酶的囊泡。出乎意料的是，Rab6A通过直接与运动结构域以及C末端相互作用来控制KIF1C的活性。细胞中驱动蛋白的缺失减缓了囊泡中所运输货物向细胞表面的运输。
实验还表明，KIF1C参与组织细胞内另一个被称为高尔基体的区室。这种作用依赖于Rab6A与驱动蛋白的N末端和C末端的结合，但不需要驱动蛋白发挥运动功能。Lee等人的发现揭示了一种驱动蛋白活性可被控制的新方式。未来的挑战将是确定其他驱动蛋白是否也以这种方式被控制，并发现Rab GTP酶在细胞中何时何地结合运动结构域。
DOI: http://dx.doi.org/10.7554/eLife.06029.002
Most kinesins transport cargoes bound to their C-termini and use N-terminal motor domains to move along microtubules. We report here a novel function for KIF1C: it transports Rab6A-vesicles and can influence Golgi complex organization. These activities correlate with KIF1C's capacity to bind the Golgi protein Rab6A directly, both via its motor domain and C-terminus. Rab6A binding to the motor domain inhibits microtubule interaction in vitro and in cells, decreasing the amount of motile KIF1C. KIF1C depletion slows protein delivery to the cell surface, interferes with vesicle motility, and triggers Golgi fragmentation. KIF1C can protect Golgi membranes from fragmentation in cells lacking an intact microtubule network. Rescue of fragmentation requires sequences that enable KIF1C to bind Rab6A at both ends, but not KIF1C motor function. Rab6A binding to KIF1C's motor domain represents an entirely new mode of regulation for a kinesin motor, and likely has important consequences for KIF1C's cellular functions. DOI: http://dx.doi.org/10.7554/eLife.06029.001 Within our cells there are many compartments that play important roles. Small bubble-like packages called vesicles carry proteins and other molecules between these compartments. These vesicles can be driven around cells by a family of motor proteins called kinesins, which move along a network of filaments called microtubules. Kinesin proteins have two sections known as the N-terminus and the C-terminus. In most cases, the N-terminus contains the motor that binds to and walks along microtubules, while the C-terminus binds to vesicles or other cell compartments. Attached to the compartments are members of another family of proteins called the Rab GTPases. These proteins help the kinesins bind to a compartment, but it was not clear if, or how, these proteins control the activity of the kinesins. Here, Lee et al. studied a kinesin called KIF1C. The experiments show that this kinesin can move vesicles that contain a Rab-GTPase called Rab6A along microtubules. Unexpectedly, Rab6A controls the activity of KIF1C by directly interacting with the motor as well as the C-terminus. Loss of the kinesin from the cell slows down the delivery of cargo carried in vesicles to the surface of the cell. The experiments also show that KIF1C is involved in organizing another compartment within cells called the Golgi. This role relies on Rab6A binding to both the N-terminus and C-terminus of the kinesin, but does not require the kinesin to act as a motor. Lee et al.'s findings reveal a new way in which the activity of kinesins can be controlled. Future challenges will be to find out if other kinesins are also controlled in this way and discover when and where the Rab GTPases bind motor domains in cells. DOI: http://dx.doi.org/10.7554/eLife.06029.002