Small stepping motion of processive dynein revealed by load-free high-speed single-particle tracking

Ando, Jun; Shima, Tomohiro; Kanazawa, Riko; Shimo-Kon, Rieko; Nakamura, Akihiko; Yamamoto, Mayuko; Kon, Takahide; Iino, Ryota

doi:10.1038/s41598-020-58070-y

Cited by 16 publications

(22 citation statements)

References 38 publications

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“…While we observed different behaviors in our simulation of a single head dynein-2, it is important to know there are any differences in the stepping mechanism between single-headed and double-headed dynein. Our results of the ratio of left- and right-side stepping is almost the same with the results of the experimental results of double headed dynein (24). Therefore, we expect no significant difference between single and double-headed dynein for the side-stepping.…”

Section: Discussionsupporting

confidence: 91%

Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation

Kubo

Bui

2022

Preprint

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Intraflagellar transport for ciliary assembly and maintenance is driven by dynein and kinesins specific for the cilia. It has been shown that anterograde and retrograde transports run on different regions of the doublet microtubule, i.e., separate train tracks. However, little is known about the regulatory mechanism of this selective process. Since the doublet microtubule is known to display specific post-translational modifications of tubulins, i.e. tubulin code, for molecular motor regulations, we investigated the motility of ciliary specific dynein-2 under different post-translational modification by coarse-grained molecular dynamics. Our setup allows us to simulate the stochastic stepping behaviors of dynein-2 on un-modified, detyrosinated, poly-glutamylated and poly-glycylated microtubules in silico. Our study revealed that poly-glutamylation can play an inhibitory effect on dynein-2 motility. Our result indicates that poly-glutamylation of the B-tubule of the doublet microtubule can be used as an efficient means to target retrograde intraflagellar transport onto the A-tubule.

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Section: Discussionsupporting

confidence: 91%

Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation

Kubo

Bui

2022

Preprint

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“…As discussed above, while most studies of dynein motors assume a purely longitudinal motion, more recent studies discovered rich transverse dynamics [37,38,52,85]. Therefore, we analyzed the NP trajectories for transverse motion as well.…”

Section: Angular/transverse Motionmentioning

confidence: 99%

“…(Using the NP translational Stokes drag coefficient, 6 , and a velocity of 4 µm/s, leads to a drag force ~10 pN, for 10 mPa s as an upper bound for the CE viscosity, which is much smaller than the typical motor force of 4 pN.). This implies that the single motor will move at its free-load velocity and without a load-sharing effect [52]; such an effect will occur only for micron-sized NPs, for which the drag force becomes significant [38,53]. Third, the cargos used in previous studies [37,38] cannot control the mechanical coupling between motors.…”

Section: Introductionmentioning

confidence: 99%

Nano-Particles Carried by Multiple Dynein Motors Self-Regulate Their Number of Actively Participating Motors

Halbi

Fayer

Aranovich

et al. 2021

IJMS

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Intra-cellular active transport by native cargos is ubiquitous. We investigate the motion of spherical nano-particles (NPs) grafted with flexible polymers that end with a nuclear localization signal peptide. This peptide allows the recruitment of several mammalian dynein motors from cytoplasmic extracts. To determine how motor–motor interactions influenced motility on the single microtubule level, we conducted bead-motility assays incorporating surface adsorbed microtubules and combined them with model simulations that were based on the properties of a single dynein. The experimental and simulation results revealed long time trajectories: when the number of NP-ligated motors Nm increased, run-times and run-lengths were enhanced and mean velocities were somewhat decreased. Moreover, the dependence of the velocity on run-time followed a universal curve, regardless of the system composition. Model simulations also demonstrated left- and right-handed helical motion and revealed self-regulation of the number of microtubule-bound, actively transporting dynein motors. This number was stochastic along trajectories and was distributed mainly between one, two, and three motors, regardless of Nm. We propose that this self-regulation allows our synthetic NPs to achieve persistent motion that is associated with major helicity. Such a helical motion might affect obstacle bypassing, which can influence active transport efficiency when facing the crowded environment of the cell.

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“…As discussed above, while most dynein motor studies assume purely longitudinal motion, more recent studies discovered rich transverse dynamics (36,37,52,53). Accordingly, we analyzed the NP trajectories for transverse motion.…”

Section: I2 Np Motility Assaysmentioning

confidence: 99%

Nano-particles carried by multiple dynein motors: A Self-Regulating Nano-Machine

Fayer

Halbi

Aranovich

et al. 2020

Preprint

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Native cargos achieve efficient intra-cellular active transport by recruiting multiple motors proteins from the cytoplasm. Here we investigate the motion of spherical nano-particles (NPs), acting as model cargos, grafted with flexible polymers, each ending with a nuclear localization signal (NLS) peptide, thereby allowing recruitment of mammalian cytoplasmic dynein. Bead-motility assays show several unique features. As the number of motors increases, the run-time and run-length increase, the longitudinal velocity mean decreases, whereas its width shows a non-monotonous behavior. Moreover, both single and multi-motor NPs perform angular (i.e., projected transverse) motion. Strikingly, the directions of angular and longitudinal motions are correlated, such that retrograde steps are combined with right-handed motion. We formulate a theoretical model to simulate the multi-dynein transported NP. The model builds on a recently theoretical description of single yeast dynein stepping on the curved microtubule surface, modified to account for mammalian dynein, and generalized to include motor-motor elastic and excluded-volume coupling. The simulation results are majorly in agreement with our experimental results. Moreover, long time trajectories exhibit both left- and right- handed helical motion around the MT symmetry axis, consistent with the measured and simulated angular velocity. The model gives further insight into the mechanism of the NP motion and suggests that the NPs are self-regulating the number of participating motors, optimizing between single motor, for obstacle bypassing, and multi-motor behavior, for persistent directional motion. We suggest that native cargos could use a similar mechanism to achieve efficient transport in the crowded cellular environment.

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Small stepping motion of processive dynein revealed by load-free high-speed single-particle tracking

Cited by 16 publications

References 38 publications

Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation

Regulatory mechanisms of the dynein-2 motility by post-translational modification revealed by MD simulation

Nano-Particles Carried by Multiple Dynein Motors Self-Regulate Their Number of Actively Participating Motors

Nano-particles carried by multiple dynein motors: A Self-Regulating Nano-Machine

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