Key Points
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The neuronal cytoskeleton is functionally specialized within distinct compartments; local differences in cytoskeletal organization regulate local traffic patterns.
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In axons, the axon initial segment serves as a filter discriminating between axonal and somatodendritic cargoes, whereas the axon shaft is a conduit for long-range transport to and from more distal synaptic sites.
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In dendrites, both the mixed microtubule polarity and the more dynamic nature of dendritic microtubules create unique challenges for efficient long-range transport and localized delivery to dendritic spines.
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These distinct regions of the neuron utilize both a common toolbox of cytoskeletal filaments and binding partners and unique complements of motors, adaptors, effectors and microtubule-associated proteins (MAPs) to provide locally specific trafficking patterns.
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Common themes are emerging, including the role of cytoskeletal polarity, the modulation of cytoskeletal tracks by post-translational modifications, the contribution of MAPs, and the precise control of multiple motors bound to the same cargo by associated adaptors and effectors.
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Further work is required to fully define the interplay between cytoskeletal organization and organelle trafficking, particularly in the AIS and in dendrites.
Abstract
Neurons are akin to modern cities in that both are dependent on robust transport mechanisms. Like the best mass transit systems, trafficking in neurons must be tailored to respond to local requirements. Neurons depend on both high-speed, long-distance transport and localized dynamics to correctly deliver cargoes and to tune synaptic responses. Here, we focus on the mechanisms that provide localized regulation of the transport machinery, including the cytoskeleton and molecular motors, to yield compartment-specific trafficking in the axon initial segment, axon terminal, dendrites and spines. The synthesis of these mechanisms provides a sophisticated and responsive transit system for the cell.
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Glossary
- Anterograde transport
-
Motor-driven transport away from the cell body, towards either the axon terminal or the distal dendrites.
- Retrograde transport
-
Motor-driven transport towards the cell body, from either the axon terminal or distal dendrites.
- Dynamic instability
-
The process through which microtubule ends dynamically switch between growing (polymerization) and shrinking (depolymerization) phases through the processes of catastrophe and recovery.
- Kinesin superfamily
-
Kinesin motors are organized into 14 families (kinesin-1 to kinesin-14) based on sequence homology, and individual kinesin proteins within these families are referred to by a KIF naming convention. Thus, a given kinesin may be referred to by its family name or protein name.
- Adaptors
-
Interacting proteins that link multiple components to form a supramolecular complex; motor adaptor proteins may promote or inhibit motility and/or the motor–cargo interaction.
- Effectors
-
Interacting proteins that promote the function and/or downstream signalling of a given target protein; motor adaptor proteins that facilitate the activity of a given motor protein are referred to as effectors.
- Processive motility
-
A process driven by one or more motors in which multiple steps in the same direction are taken in a continuous manner without dissociation from the motor track.
- F-Actin
-
Globular actin monomers (G-actin) polymerize to form filamentous F-actin.
- Silicon rhodamine actin
-
(SiR actin). A conjugate of the far-red fluorophore silicon rhodamine (SiR) and the F-actin-binding and stabilizing toxin jasplakinolide, which allows for live-cell imaging using conventional or super-resolution microscopy.
- Nucleation
-
The process of initiating de novo filament polymerization, usually with the help of nucleator proteins including, but not limited to, actin-related protein 2 (ARP2), ARP3 and formins for actin and γ-tubulin ring complex (γ-TuRC) for microtubules. This process is distinct from templated growth, in which a small seed of an existing filament serves as a point for filament elongation.
- Phalloidin
-
A fungal toxin that binds to F-actin; fluorescently tagged phalloidin derivatives are used to visualize F-actin in fixed preparations.
- Cytoskeletal dynamics
-
A broad term that describes the continuous process of cytoskeletal filament assembly and disassembly.
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Nirschl, J., Ghiretti, A. & Holzbaur, E. The impact of cytoskeletal organization on the local regulation of neuronal transport. Nat Rev Neurosci 18, 585–597 (2017). https://doi.org/10.1038/nrn.2017.100
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DOI: https://doi.org/10.1038/nrn.2017.100
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