Kinesin and dynein use distinct mechanisms to bypass obstacles

Abstract

Kinesin-1 and cytoplasmic dynein are microtubule (MT) motors that transport intracellular cargoes. It remains unclear how these motors move along MTs densely coated with obstacles of various sizes in the cytoplasm. Here, we tested the ability of single and multiple motors to bypass synthetic obstacles on MTs in vitro. Contrary to previous reports, we found that single mammalian dynein is highly capable of bypassing obstacles. Single human kinesin-1 motors fail to avoid obstacles, consistent with their inability to take sideways steps on to neighboring MT protofilaments. Kinesins overcome this limitation when working in teams, bypassing obstacles as effectively as multiple dyneins. Cargos driven by multiple kinesins or dyneins are also capable of rotating around the MT to bypass large obstacles. These results suggest that multiplicity of motors is required not only for transporting cargos over long distances and generating higher forces, but also for maneuvering cargos on obstacle-coated MT surfaces.

Optimal sidestepping of intraflagellar transport kinesins regulates structure and function of sensory cilia

“…Intriguingly, these linear motor proteins do not always follow a strictly linear path along actin filaments or microtubules (MTs). They also produce force perpendicular to their direction of movement, generating sidesteps or off-axis movement along their filamentous tracks (Ricca & Rock, 2010;Brunnbauer et al, 2012;Ferro et al, 2019). Torque generation of motor proteins was first demonstrated by the purified Tetrahymena axonemal dynein, which rotates the microtubules around their axes while translocating them (Vale & Toyoshima, 1988).…”

“…Torque generation of motor proteins was first demonstrated by the purified Tetrahymena axonemal dynein, which rotates the microtubules around their axes while translocating them (Vale & Toyoshima, 1988). Subsequently, in vitro studies revealed that such torsional and axial force generation appears to be a prevalent feature for all three families of molecular motors (Nishizaka et al, 1993;Yajima & Cross, 2005;Beausang et al, 2008;Yajima et al, 2008;Ricca & Rock, 2010;Brunnbauer et al, 2012;Can et al, 2014;Ferro et al, 2019). However, it remains unclear whether motor proteins take sidesteps and generate torque in a living cell.…”

Mitochondria-adaptor TRAK1 promotes kinesin-1 driven transport in crowded environments

“…Microtubule surfaces in cells are crowded by numerous microtubule-associated proteins, which act as obstacles for processively moving molecular motors. When kinesin-1 encounters an obstacle, its run length decreases as kinesin-1 is more likely to dissociate from the microtubule 30,49 than to continue its run by switching the protofilaments by side-stepping and circumventing the obstacle 31 . In vitro single molecule experiments in cell lysate imitate the physiological state of microtubules crowded with microtubule associated proteins 30,59 , while rigor-binding kinesin-1 mutants provide static roadblocks masking the kinesin-1 binding sites 31 .…”

“…7 The microtubule surface in cells is crowded with numerous microtubule-associated proteins hindering the motion of molecular motors. Crowding of the microtubule surface results in a drastic shortening of the run length of kinesin-1 30,31,49,50 . Since we observed that TRAK1 increased the processivity of KIF5B, we wondered whether TRAK1 can extend the movement range of kinesin-1 in crowded conditions.…”

Mitotic Poisons in Research and Medicine

“…Microtubules are essential for maintaining the cell shape, polarity, migration and division [ 5 ]. Furthermore, they are utilized by protein motors kinesins and dyneins to transport molecules inside a cell [ 8 ].…”