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The Neuron Navigators: Structure, function, and evolutionary history
Neuron navigators (Navigators) are cytoskeletal-associated proteins important for neuron migration, neurite growth, and axon guidance, but they also function more widely in other tissues. Recent studies have revealed novel cellular functions of Navigators such as macropinocytosis, and have implicate...
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2023
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877351/ https://www.ncbi.nlm.nih.gov/pubmed/36710926 http://dx.doi.org/10.3389/fnmol.2022.1099554 |
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author | Powers, Regina M. Hevner, Robert F. Halpain, Shelley |
author_facet | Powers, Regina M. Hevner, Robert F. Halpain, Shelley |
author_sort | Powers, Regina M. |
collection | PubMed |
description | Neuron navigators (Navigators) are cytoskeletal-associated proteins important for neuron migration, neurite growth, and axon guidance, but they also function more widely in other tissues. Recent studies have revealed novel cellular functions of Navigators such as macropinocytosis, and have implicated Navigators in human disorders of axon growth. Navigators are present in most or all bilaterian animals: vertebrates have three Navigators (NAV1-3), Drosophila has one (Sickie), and Caenorhabditis elegans has one (Unc-53). Structurally, Navigators have conserved N- and C-terminal regions each containing specific domains. The N-terminal region contains a calponin homology (CH) domain and one or more SxIP motifs, thought to interact with the actin cytoskeleton and mediate localization to microtubule plus-end binding proteins, respectively. The C-terminal region contains two coiled-coil domains, followed by a AAA+ family nucleoside triphosphatase domain of unknown activity. The Navigators appear to have evolved by fusion of N- and C-terminal region homologs present in simpler organisms. Overall, Navigators participate in the cytoskeletal response to extracellular cues via microtubules and actin filaments, in conjunction with membrane trafficking. We propose that uptake of fluid-phase cues and nutrients and/or downregulation of cell surface receptors could represent general mechanisms that explain Navigator functions. Future studies developing new models, such as conditional knockout mice or human cerebral organoids may reveal new insights into Navigator function. Importantly, further biochemical studies are needed to define the activities of the Navigator AAA+ domain, and to study potential interactions among different Navigators and their binding partners. |
format | Online Article Text |
id | pubmed-9877351 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-98773512023-01-27 The Neuron Navigators: Structure, function, and evolutionary history Powers, Regina M. Hevner, Robert F. Halpain, Shelley Front Mol Neurosci Molecular Neuroscience Neuron navigators (Navigators) are cytoskeletal-associated proteins important for neuron migration, neurite growth, and axon guidance, but they also function more widely in other tissues. Recent studies have revealed novel cellular functions of Navigators such as macropinocytosis, and have implicated Navigators in human disorders of axon growth. Navigators are present in most or all bilaterian animals: vertebrates have three Navigators (NAV1-3), Drosophila has one (Sickie), and Caenorhabditis elegans has one (Unc-53). Structurally, Navigators have conserved N- and C-terminal regions each containing specific domains. The N-terminal region contains a calponin homology (CH) domain and one or more SxIP motifs, thought to interact with the actin cytoskeleton and mediate localization to microtubule plus-end binding proteins, respectively. The C-terminal region contains two coiled-coil domains, followed by a AAA+ family nucleoside triphosphatase domain of unknown activity. The Navigators appear to have evolved by fusion of N- and C-terminal region homologs present in simpler organisms. Overall, Navigators participate in the cytoskeletal response to extracellular cues via microtubules and actin filaments, in conjunction with membrane trafficking. We propose that uptake of fluid-phase cues and nutrients and/or downregulation of cell surface receptors could represent general mechanisms that explain Navigator functions. Future studies developing new models, such as conditional knockout mice or human cerebral organoids may reveal new insights into Navigator function. Importantly, further biochemical studies are needed to define the activities of the Navigator AAA+ domain, and to study potential interactions among different Navigators and their binding partners. Frontiers Media S.A. 2023-01-12 /pmc/articles/PMC9877351/ /pubmed/36710926 http://dx.doi.org/10.3389/fnmol.2022.1099554 Text en Copyright © 2023 Powers, Hevner and Halpain. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Molecular Neuroscience Powers, Regina M. Hevner, Robert F. Halpain, Shelley The Neuron Navigators: Structure, function, and evolutionary history |
title | The Neuron Navigators: Structure, function, and evolutionary history |
title_full | The Neuron Navigators: Structure, function, and evolutionary history |
title_fullStr | The Neuron Navigators: Structure, function, and evolutionary history |
title_full_unstemmed | The Neuron Navigators: Structure, function, and evolutionary history |
title_short | The Neuron Navigators: Structure, function, and evolutionary history |
title_sort | neuron navigators: structure, function, and evolutionary history |
topic | Molecular Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9877351/ https://www.ncbi.nlm.nih.gov/pubmed/36710926 http://dx.doi.org/10.3389/fnmol.2022.1099554 |
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