How Molecular Motors Are Arranged on a Cargo Is Important for Vesicular Transport

Abstract

The spatial organization of the cell depends upon intracellular trafficking of cargos hauled along microtubules and actin filaments by the molecular motor proteins kinesin, dynein, and myosin. Although much is known about how single motors function, there is significant evidence that cargos in vivo are carried by multiple motors. While some aspects of multiple motor function have received attention, how the cargo itself —and motor organization on the cargo—affects transport has not been considered. To address this, we have developed a three-dimensional Monte Carlo simulation of motors transporting a spherical cargo, subject to thermal fluctuations that produce both rotational and translational diffusion. We found that these fluctuations could exert a load on the motor(s), significantly decreasing the mean travel distance and velocity of large cargos, especially at large viscosities. In addition, the presence of the cargo could dramatically help the motor to bind productively to the microtubule: the relatively slow translational and rotational diffusion of moderately sized cargos gave the motors ample opportunity to bind to a microtubule before the motor/cargo ensemble diffuses out of range of that microtubule. For rapidly diffusing cargos, the probability of their binding to a microtubule was high if there were nearby microtubules that they could easily reach by translational diffusion. Our simulations found that one reason why motors may be approximately 100 nm long is to improve their ‘on’ rates when attached to comparably sized cargos. Finally, our results suggested that to efficiently regulate the number of active motors, motors should be clustered together rather than spread randomly over the surface of the cargo. While our simulation uses the specific parameters for kinesin, these effects result from generic properties of the motors, cargos, and filaments, so they should apply to other motors as well.

Measuring collective transport by defined numbers of processive and nonprocessive kinesin motors

“…Previous studies on collective transport have mainly focused on processive motors, and our results for processive kinesin-1 at low load are generally consistent with previously proposed theories (14,(16)(17)(18). However, we made unexpected observations when a load was imposed, and report the distinct properties of nonprocessive motors that might be required for efficient collective transport.…”

“…It seems plausible to suppose that, when a motor is tethered to a MT via a linker, one with a shorter linker would find the binding sites more quickly, thereby increasing the binding time. Most recently, Erickson et al have predicted that the onrate of cargo-bound motors is strongly affected by the motor organization on a cargo and that the on-rate is inversely proportional to a power of the motor length (18). We therefore assumed that the on-rate was similarly dependent on the intermotor spacing, which successfully reproduced the experimental observations for two coupled Ncds (Fig.…”

Translocating myonuclei have distinct leading and lagging edges that require Kinesin and Dynein

“…The proximity of adjacent nuclei might produce local asymmetries in MT organization, which then causes Kinesin activity to cluster at the front of the nucleus and Dynein activity to cluster at the back. Indeed, clustering of motors has been proposed as a means to increase efficiency for moving large cargos (Erickson et al, 2011), but this is a question that requires more extensive analysis as it is complicated by the clustered nature of myonuclei during these movements. Alternatively, a signaling gradient from the muscle pole could provide a cue that activates Kinesin, or deactivates Dynein, on the front of the nucleus.…”

Elastic Coupling Effects in Cooperative Transport by a Pair of Molecular Motors

“…[50][51][52] In addition, several groups have developed models that include detailed descriptions of the single motors involved and that address specific effects such as the stochasticity of stepping 19,41,42 and the geometry of motor assemblies. 13,20,21,40 As in the experimental studies listed above, the focus of recent theoretical work has been on assemblies of two motor molecules. In particular, several recent studies have addressed the model case of two coupled kinesin-1 motors.…”