Role of actin in organelle trafficking in neurons

Abstract

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.

Impaired Mitochondrial Mobility in Charcot-Marie-Tooth Disease

“…All INF2 CMT mutations are predicted or have been shown to increase actin assembly (Bayraktar et al, 2020). While some actin-binding motor proteins likely facilitate microtubule-independent mitochondrial transport, numerous studies have shown that long-range microtubule-based mobility of mitochondria is antagonized by actin and actin-binding motor proteins (Chada and Hollenbeck, 2004;Quintero et al, 2009;Pathak et al, 2010;Venkatesh et al, 2019;Cardanho-Ramos et al, 2020). Thus, while the effects of INF2 CMT mutations have yet to be studied in neurons, it is reasonable to expect that INF2 CMT mutations will cause an actin-dependent decrease in mitochondrial mobility in axons.…”

Cytoskeletal regulation guides neuronal trafficking to effectively supply the synapse

“…While the bulk of long-distance neuronal trafficking is mediated by the microtubule cytoskeleton, actin and myosin also play important roles in synaptic function, including organelle biogenesis, organelle transport driven by either actin polymerization or myosin motors, localized cargo anchoring, and physical barriers to halt cargo motility (discussed more thoroughly in the following recent reviews [144][145][146] ). Of note, polarized actin filaments may help define the dendritic cargo-restricting axon initial segment (AIS) 147 .…”

“…Whether this mechanism is conserved in the dendritic compartment has yet to be determined. (For additional information on neuronal and synaptic actin-myosin regulation, we direct the reader to the following reviews 144,156,157 . )…”

Molecular mechanisms governing axonal transport: a C. elegans perspective

“…Neuronal actin assemblies have been reported to assist longdistance transport of cargo in axons and dendrites (Venkatesh, Mathew, & Koushika, 2020). In neuronal processes, actin is present as waves, rings, polarized patches, trails, hotspots, bundled filopodial structures, and dendritic networks, several of which have been covered extensively in the following reviews (Roy, 2020;Venkatesh et al, 2020). The first in vivo demonstration of actin trails and hot spots were made in the touch receptor neurons of C. elegans (Sood et al, 2018).…”