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Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners

Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this...

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Autores principales: Homma, Yuta, Fukuda, Mitsunori
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927283/
https://www.ncbi.nlm.nih.gov/pubmed/27170183
http://dx.doi.org/10.1091/mbc.E16-02-0091
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author Homma, Yuta
Fukuda, Mitsunori
author_facet Homma, Yuta
Fukuda, Mitsunori
author_sort Homma, Yuta
collection PubMed
description Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this process, their regulatory mechanisms during neurite outgrowth are poorly understood. Here, we show that Rabin8, a Rab8-guanine nucleotide exchange factor (GEF), regulates nerve growth factor (NGF)–induced neurite outgrowth of PC12 cells. Knockdown of Rabin8 results in inhibition of neurite outgrowth, whereas overexpression promotes it. We also find that Rab10 is a novel substrate of Rabin8 and that both Rab8 and Rab10 function during neurite outgrowth downstream of Rabin8. Surprisingly, however, a GEF activity–deficient isoform of Rabin8 also promotes neurite outgrowth, indicating the existence of a GEF activity–independent role of Rabin8. The Arf6/Rab8-positive recycling endosomes (Arf6/Rab8-REs) and Rab10/Rab11-positive REs (Rab10/Rab11-REs) in NGF-stimulated PC12 cells are differently distributed. Rabin8 localizes on both RE populations and appears to activate Rab8 and Rab10 there. These localizations and functions of Rabin8 are Rab11 dependent. Thus Rabin8 regulates neurite outgrowth both by coordinating with Rab8, Rab10, and Rab11 and by a GEF activity–independent mechanism.
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spelling pubmed-49272832016-09-16 Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners Homma, Yuta Fukuda, Mitsunori Mol Biol Cell Articles Many aspects of membrane-trafficking events are regulated by Rab-family small GTPases. Neurite outgrowth requires massive addition of proteins and lipids to the tips of growing neurites by membrane trafficking, and although several Rabs, including Rab8, Rab10, and Rab11, have been implicated in this process, their regulatory mechanisms during neurite outgrowth are poorly understood. Here, we show that Rabin8, a Rab8-guanine nucleotide exchange factor (GEF), regulates nerve growth factor (NGF)–induced neurite outgrowth of PC12 cells. Knockdown of Rabin8 results in inhibition of neurite outgrowth, whereas overexpression promotes it. We also find that Rab10 is a novel substrate of Rabin8 and that both Rab8 and Rab10 function during neurite outgrowth downstream of Rabin8. Surprisingly, however, a GEF activity–deficient isoform of Rabin8 also promotes neurite outgrowth, indicating the existence of a GEF activity–independent role of Rabin8. The Arf6/Rab8-positive recycling endosomes (Arf6/Rab8-REs) and Rab10/Rab11-positive REs (Rab10/Rab11-REs) in NGF-stimulated PC12 cells are differently distributed. Rabin8 localizes on both RE populations and appears to activate Rab8 and Rab10 there. These localizations and functions of Rabin8 are Rab11 dependent. Thus Rabin8 regulates neurite outgrowth both by coordinating with Rab8, Rab10, and Rab11 and by a GEF activity–independent mechanism. The American Society for Cell Biology 2016-07-01 /pmc/articles/PMC4927283/ /pubmed/27170183 http://dx.doi.org/10.1091/mbc.E16-02-0091 Text en © 2016 Homma and Fukuda. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Homma, Yuta
Fukuda, Mitsunori
Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title_full Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title_fullStr Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title_full_unstemmed Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title_short Rabin8 regulates neurite outgrowth in both GEF activity–dependent and –independent manners
title_sort rabin8 regulates neurite outgrowth in both gef activity–dependent and –independent manners
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4927283/
https://www.ncbi.nlm.nih.gov/pubmed/27170183
http://dx.doi.org/10.1091/mbc.E16-02-0091
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