The University of Southampton
University of Southampton Institutional Repository

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
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
2073-4409
Steele-Nicholson, Lloyd J.
f6ff7414-aea5-4648-8152-4143c69087d7
Andrews, Melissa R.
ae987a2f-878e-4ae3-a7a3-a7170712096c
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).

Record type: Article

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.

Text
cells-11-00937-v3 - Version of Record
Available under License Creative Commons Attribution.
Download (2MB)

More information

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
ORCID for Melissa R. Andrews: ORCID iD orcid.org/0000-0001-5960-5619

Catalogue record

Date deposited: 11 Apr 2022 17:49
Last modified: 17 Mar 2024 03:44

Export record

Altmetrics

Download statistics

Downloads from ePrints over the past year. Other digital versions may also be available to download e.g. from the publisher's website.

View more statistics

Atom RSS 1.0 RSS 2.0

Contact ePrints Soton: eprints@soton.ac.uk

ePrints Soton supports OAI 2.0 with a base URL of http://eprints.soton.ac.uk/cgi/oai2

This repository has been built using EPrints software, developed at the University of Southampton, but available to everyone to use.

We use cookies to ensure that we give you the best experience on our website. If you continue without changing your settings, we will assume that you are happy to receive cookies on the University of Southampton website.

×