Biophysics Program, Stanford University, Stanford, CA 94305.
Department of Physics, Stanford University, Stanford, CA 94305.
Proc Natl Acad Sci U S A. 2017 Aug 15;114(33):E6830-E6838. doi: 10.1073/pnas.1708157114. Epub 2017 Jul 31.
Homodimeric KIF17 and heterotrimeric KIF3AB are processive, kinesin-2 family motors that act jointly to carry out anterograde intraflagellar transport (IFT), ferrying cargo along microtubules (MTs) toward the tips of cilia. How IFT trains attain speeds that exceed the unloaded rate of the slower, KIF3AB motor remains unknown. By characterizing the motility properties of kinesin-2 motors as a function of load we find that the increase in KIF3AB velocity, elicited by forward loads from KIF17 motors, cannot alone account for the speed of IFT trains in vivo. Instead, higher IFT velocities arise from an increased likelihood that KIF3AB motors dissociate from the MT, resulting in transport by KIF17 motors alone, unencumbered by opposition from KIF3AB. The rate of transport is therefore set by an equilibrium between a faster state, where only KIF17 motors move the train, and a slower state, where at least one KIF3AB motor on the train remains active in transport. The more frequently the faster state is accessed, the higher the overall velocity of the IFT train. We conclude that IFT velocity is governed by () the absolute numbers of each motor type on a given train, () how prone KIF3AB is to dissociation from MTs relative to KIF17, and () how prone both motors are to dissociation relative to binding MTs.
二聚体 KIF17 和三聚体 KIF3AB 是进行性的、驱动蛋白-2 家族的马达，它们共同作用进行顺向鞭毛内运输 (IFT)，将货物沿着微管 (MT) 运送到纤毛的顶端。IFT 列车如何达到超过较慢的 KIF3AB 马达空载速度的速度仍然未知。通过描述 KIF2 马达在负载下的运动特性，我们发现，由 KIF17 马达施加的前向负载引起的 KIF3AB 速度增加，不能单独解释 IFT 列车在体内的速度。相反，更高的 IFT 速度源于 KIF3AB 马达从 MT 解离的可能性增加，导致仅由 KIF17 马达驱动运输，不受 KIF3AB 的阻碍。因此，运输的速度取决于一个更快的状态和一个更慢的状态之间的平衡，在这个更快的状态中，只有 KIF17 马达移动列车，而在这个更慢的状态中，列车上至少有一个 KIF3AB 马达在运输中保持活跃。访问更快状态的频率越高，IFT 列车的整体速度就越高。我们得出结论，IFT 速度由以下因素决定：()给定列车上每种马达类型的绝对数量，()KIF3AB 相对于 KIF17 从 MT 解离的倾向，以及()两个马达相对于结合 MT 解离的倾向。
