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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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Autores principales: Powers, Regina M., Hevner, Robert F., Halpain, Shelley
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
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.
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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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