Department of Genetics, Harvard Medical School, Boston, MA 02115.
Department of Molecular Biology, Massachusetts General Hospital, Boston, MA 02114.
Proc Natl Acad Sci U S A. 2022 Jul 12;119(28):e2120193119. doi: 10.1073/pnas.2120193119. Epub 2022 Jul 7.
Coupling of motor proteins within arrays drives muscle contraction, flagellar beating, chromosome segregation, and other biological processes. Current models of motor coupling invoke either direct mechanical linkage or protein crowding, which rely on short-range motor-motor interactions. In contrast, coupling mechanisms that act at longer length scales remain largely unexplored. Here we report that microtubules can physically couple motor movement in the absence of detectable short-range interactions. The human kinesin-4 Kif4A changes the run length and velocity of other motors on the same microtubule in the dilute binding limit, when approximately 10-nm-sized motors are much farther apart than the motor size. This effect does not depend on specific motor-motor interactions because similar changes in Kif4A motility are induced by kinesin-1 motors. A micrometer-scale attractive interaction potential between motors is sufficient to recreate the experimental results in a biophysical model. Unexpectedly, our theory suggests that long-range microtubule-mediated coupling affects not only binding kinetics but also motor mechanochemistry. Therefore, the model predicts that motors can sense and respond to motors bound several micrometers away on a microtubule. Our results are consistent with a paradigm in which long-range motor interactions along the microtubule enable additional forms of collective motor behavior, possibly due to changes in the microtubule lattice.
马达蛋白在阵列中的偶联驱动肌肉收缩、鞭毛运动、染色体分离和其他生物过程。马达偶联的当前模型援引了直接的机械连接或蛋白质拥挤,这依赖于短程马达-马达相互作用。相比之下,在更长的尺度上起作用的偶联机制在很大程度上仍未被探索。在这里,我们报告说,微管可以在没有可检测的短程相互作用的情况下物理地偶联马达运动。在稀释结合极限下,人类的驱动蛋白-4(Kif4A)改变了同一微管上其他马达的运行长度和速度,此时大约 10nm 大小的马达彼此之间的距离远远超过马达的大小。这种效应不依赖于特定的马达-马达相互作用,因为驱动蛋白-1 马达也能诱导 Kif4A 运动性的类似变化。马达之间的微米级吸引力相互作用势能足以在生物物理模型中重现实验结果。出乎意料的是,我们的理论表明,长程微管介导的偶联不仅影响结合动力学,还影响马达机械化学。因此,该模型预测,马达可以感知和响应绑定在微管上几微米远的马达。我们的结果与一个范例一致,即微管上的长程马达相互作用使额外形式的集体马达行为成为可能,这可能是由于微管晶格的变化。