Axon-targeting motifs: Mechanisms and applications of enhancing axonal localisation of transmembrane proteins
Axon-targeting motifs: Mechanisms and applications of enhancing axonal localisation of transmembrane proteins
Neuronal polarity established in developing neurons ensures proper function in the mature nervous system. As functionally distinct cellular compartments, axons and dendrites often require different subsets of proteins to maintain synaptic transmission and overall order. Although neurons in the mature CNS do not regenerate throughout life, their interactions with their extracellular environment are dynamic. The axon remains an overall protected area of the neuron where only certain proteins have access throughout the lifespan of the cell. This is in comparison to the somatodendritic compartment, where although it too has a specialised subset of proteins required for its maintenance, many proteins destined for the axonal compartment must first be trafficked through the former. Recent research has shown that axonal proteins contain specific axon-targeting motifs that permit access to the axonal compartment as well as downstream targeting to the axonal membrane. These motifs target proteins to the axonal compartment by a variety of mechanisms including: promoting segregation into axon-targeted secretory vesicles, increasing interaction with axonal kinesins and enhancing somatodendritic endocytosis. In this review, we will discuss axon-targeting motifs within the context of established neuron trafficking mechanisms. We will also include examples of how these motifs have been applied to target proteins to the axonal compartment to improve both tools for the study of axon biology, and for use as potential therapeutics for axonopathies.
Axon transport, Axon-targeting motif, Neuronal polarity, Protein trafficking, Secretory pathway, Somatodendritic, Transcytosis, Transmem-brane protein
Steele-Nicholson, Lloyd J.
f6ff7414-aea5-4648-8152-4143c69087d7
Andrews, Melissa R.
ae987a2f-878e-4ae3-a7a3-a7170712096c
9 March 2022
Steele-Nicholson, Lloyd J.
f6ff7414-aea5-4648-8152-4143c69087d7
Andrews, Melissa R.
ae987a2f-878e-4ae3-a7a3-a7170712096c
Steele-Nicholson, Lloyd J. and Andrews, Melissa R.
(2022)
Axon-targeting motifs: Mechanisms and applications of enhancing axonal localisation of transmembrane proteins.
Cells, 11 (6), [937].
(doi:10.3390/cells11060937).
Abstract
Neuronal polarity established in developing neurons ensures proper function in the mature nervous system. As functionally distinct cellular compartments, axons and dendrites often require different subsets of proteins to maintain synaptic transmission and overall order. Although neurons in the mature CNS do not regenerate throughout life, their interactions with their extracellular environment are dynamic. The axon remains an overall protected area of the neuron where only certain proteins have access throughout the lifespan of the cell. This is in comparison to the somatodendritic compartment, where although it too has a specialised subset of proteins required for its maintenance, many proteins destined for the axonal compartment must first be trafficked through the former. Recent research has shown that axonal proteins contain specific axon-targeting motifs that permit access to the axonal compartment as well as downstream targeting to the axonal membrane. These motifs target proteins to the axonal compartment by a variety of mechanisms including: promoting segregation into axon-targeted secretory vesicles, increasing interaction with axonal kinesins and enhancing somatodendritic endocytosis. In this review, we will discuss axon-targeting motifs within the context of established neuron trafficking mechanisms. We will also include examples of how these motifs have been applied to target proteins to the axonal compartment to improve both tools for the study of axon biology, and for use as potential therapeutics for axonopathies.
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cells-11-00937-v3
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Accepted/In Press date: 7 March 2022
e-pub ahead of print date: 9 March 2022
Published date: 9 March 2022
Additional Information:
Funding Information:
Funding: L.J.S.-N. is supported by a studentship from the Gerald Kerkut Charitable Trust. M.R.A. is supported by a research grant from the Biotechnology and Biological Sciences Research Council (BBSRC) (Grant: BBN008189/1) and the International Foundation for Research in Paraplegia (IRP) (Grant: P182).
Publisher Copyright:
© 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Keywords:
Axon transport, Axon-targeting motif, Neuronal polarity, Protein trafficking, Secretory pathway, Somatodendritic, Transcytosis, Transmem-brane protein
Identifiers
Local EPrints ID: 455990
URI: http://eprints.soton.ac.uk/id/eprint/455990
ISSN: 2073-4409
PURE UUID: d86a4aa2-353b-47d3-9ef2-139d9e093bf7
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Date deposited: 11 Apr 2022 17:49
Last modified: 13 Jun 2024 01:57
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