Cooperative protofilament switching emerges from inter-motor interference in multiple-motor transport

Ando, David; Mattson, Michelle K.; Xu, Jing; Gopinathan, Ajay

doi:10.1038/srep07255

Cited by 14 publications

(15 citation statements)

References 43 publications

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“…We next examined vesicle pausing behavior along the axon and inside synaptic boutons (see Supplemental Experimental Procedures Appendix 1 for details). Vesicle pausing during axonal transport is a common phenomenon and has been of significant interest because it is believed to reflect multi-motor coordination (Ando et al, 2014). Consistent with the characteristics of axonal transport of other organelles (Chen and Sheng, 2013), synaptic vesicles underwent frequent pausing in the axons in CT conditions (Figures 1A and 1H).…”

Section: Actin Network and Myosin V Support Vesicle Motility During Isvementioning

confidence: 60%

Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons

Gramlich

Klyachko

2017

Cell Reports

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Vesicle sharing between synaptic boutons is an important component of the recycling process that synapses employ to maintain vesicle pools. However, the mechanisms supporting and regulating vesicle transport during the inter-synaptic exchange remain poorly understood. Using nanometer-resolution tracking of individual synaptic vesicles and advanced computational algorithms, we find that long-distance axonal transport of synaptic vesicles between hippocampal boutons is partially mediated by the actin network, with myosin V as the primary actin-dependent motor that drives this vesicle transport. Furthermore, we find that vesicle exit from the synapse to the axon and long-distance vesicle transport are both rapidly and dynamically regulated by activity. We corroborated these findings with two complementary modeling approaches of vesicle exit, which closely reproduced experimental observations. These findings uncover the roles of actin and myosin V in supporting the inter-synaptic vesicle exchange and reveal that this process is dynamically modulated in an activity-dependent manner.

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Section: Actin Network and Myosin V Support Vesicle Motility During Isvementioning

confidence: 60%

Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons

Gramlich

Klyachko

2017

Cell Reports

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“…We carried out simulations at zero viscous drag to test this possibility. As experimental measurements of the stiffness of molecular motors (or other proteins) are still limited, here we examined a large, 100-fold range of values of motor stiffness, including available in vitro experimental measurements for single-kinesin transport 32 and multiple-motor transport 33 – 35 .…”

Section: Resultsmentioning

confidence: 99%

“…Our findings at the single-molecule level are likely directly relevant for transport by small teams of kinesin-1, which is on average accomplished via the action of a single kinesin 48 – 50 . Thermal diffusion of multiple-motor cargos depends stochastically on the number of motors linking the cargo to the microtubule 33 – 35 . Because we did not detect a strong impact of motor stiffness on the shortening effect of cargo diffusion on run length (Fig.…”

Section: Discussionmentioning

confidence: 99%

Cargo diffusion shortens single-kinesin runs at low viscous drag

Wilson

Quint

Gopinathan

et al. 2019

Sci Rep

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Molecular motors such as kinesin-1 drive active, long-range transport of cargos along microtubules in cells. Thermal diffusion of the cargo can impose a randomly directed, fluctuating mechanical load on the motor carrying the cargo. Recent experiments highlighted a strong asymmetry in the sensitivity of single-kinesin run length to load direction, raising the intriguing possibility that cargo diffusion may non-trivially influence motor run length. To test this possibility, here we employed Monte Carlo-based simulations to evaluate the transport of cargo by a single kinesin. Our simulations included physiologically relevant viscous drag on the cargo and interrogated a large parameter space of cytoplasmic viscosities, cargo sizes, and motor velocities that captures their respective ranges in living cells. We found that cargo diffusion significantly shortens single-kinesin runs. This diffusion-based shortening is countered by viscous drag, leading to an unexpected, non-monotonic variation in run length as viscous drag increases. To our knowledge, this is the first identification of a significant effect of cargo diffusion on motor-based transport. Our study highlights the importance of cargo diffusion and load-detachment kinetics on single-motor functions under physiologically relevant conditions.

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“…UCSF Tomo was used to collect tilt-series and 3-D reconstructions were carried out using a weighted back-projection algorithm tracking 10 nm fiducials in IMOD. We estimate the resolution in our reconstructions to be approximately 5.6 nm based on our ability to resolve the lateral spacing of protofilaments [20] comprising the microtubules found within the tomograms (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Direct visualization of vaults within intact cells by electron cryo-tomography

Woodward

Mendonça

Jensen

2015

Cell. Mol. Life Sci.

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The vault complex is the largest cellular ribonucleoprotein complex ever characterized and is present across diverse Eukarya. Despite significant information regarding the structure, composition and evolutionary conservation of the vault, little is know about the complex’s actual biological function. To determine if intracellular vaults are morphologically similar to previously studied purified and recombinant vaults, we have used electron cryo-tomography to characterize the vault complexes found in the thin edges of primary human cells growing in tissue culture. Our studies confirm that intracellular vaults are similar in overall size and shape to purified and recombinant vaults previously analyzed. Results from subtomogram averaging indicate that densities within the vault lumen are not ordered, but randomly distributed. We also observe that vaults located in the extreme periphery of the cytoplasm predominately associate with granule-like structures and actin. Our ultrastructure studies augment existing biochemical, structural and genetic information on the vault, and provide important intracellular context for the ongoing efforts to understand the biological function of the native cytoplasmic vault.

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Cooperative protofilament switching emerges from inter-motor interference in multiple-motor transport

Cited by 14 publications

References 43 publications

Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons

Actin/Myosin-V- and Activity-Dependent Inter-synaptic Vesicle Exchange in Central Neurons

Cargo diffusion shortens single-kinesin runs at low viscous drag

Direct visualization of vaults within intact cells by electron cryo-tomography

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