Actin is a major cytoskeletal element involved in multiple cellular processes. Actin‐rich regions present along the neuronal process aid in neuronal function, mediating multiple events involved in organelle trafficking. Actin is involved in organelle biogenesis, transport, and anchoring at specific locations. These functions can potentially be regulated by actin in a myosin‐dependent or myosin‐independent manner. The actin network could aid in membrane remodeling through membrane constriction, motor dependent transport, polymerization‐based transport, cargo anchoring, and halting of cargo by acting as a physical barrier. Additionally, actin dynamics is perturbed in some neurodegenerative diseases where it could impact organelle biogenesis, transport, or anchoring thereby contributing to progression of disease phenotypes. The role of actin and myosin in organelle trafficking is the primary focus of this review.

Stationary clusters of vesicles are a prominent feature of axonal transport, but little is known about their physiological and functional relevance to axonal transport. We investigate the role of vesicle motility characteristics in modulating the formation and lifetimes of such stationary clusters, and their effect on cargo flow. We develop a simulation model describing key features of axonal cargo transport, benchmarking the model against experiments in the Posterior Lateral Mechanosensory (PLM) neurons of C. elegans. Our simulations include multiple microtubule tracks, varied cargo motion states and accounts for dynamic cargo-cargo interactions. Our model also incorporates static obstacles to vesicle transport in the form of microtubule ends, stalled vesicles, and stationary mitochondria. We demonstrate, both in simulations and in an experimental system, that a reduction in reversal rates is associated with a higher proportion of long-lived stationary vesicle clusters and reduced net anterograde transport. Our simulations support the view that stationary clusters function as dynamic reservoirs of cargo vesicles, and reversals aid cargo in navigating obstacles and regulate cargo transport by modulating the proportion of stationary vesicle clusters along the neuronal process.

Molecular motors drive the directed transport of presynaptic vesicles along the narrow axons of nerve cells. Stationary clusters of such vesicles are a prominent feature of axonal transport, but little is known about their physiological and functional relevance. Here, we develop a simulation model describing key features of axonal cargo transport with a view to addressing this question, benchmarking the model against our experiments in the touch neurons of C. elegans. Our simulations provide for multiple microtubule tracks and varied cargo motion states while also incorporating cargo-cargo interactions. Our model also incorporates obstacles to vesicle transport in the form of microtubule ends, stalled vesicles, and stationary mitochondria. We devise computational methodologies to simulate both axonal bleaching and axotomy, showing that our results reproduce the properties of both moving as well as stationary cargo in vivo. Increasing vesicle numbers leads to larger and more long-lived stationary clusters of vesicular cargo. Vesicle clusters are dynamically stable, explaining why they are ubiquitously seen. Modulating the rates of cargo motion-state switching allows cluster lifetimes and flux to be tuned both in simulations and experiments. We demonstrate, both in simulations and in an experimental system, that suppressing reversals leads to larger stationary vesicle clusters being formed while also reducing flux. Our simulation results support the view that the physiological significance of clusters is located in their role as dynamic reservoirs of cargo vesicles, capable of being released or sequestered on demand.

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