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A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner
Precise wiring patterns of axons are among the remarkable features of neuronal circuit formation, and establishment of the proper neuronal network requires control of outgrowth, branching, and guidance of axons. R-Ras is a Ras-family small GTPase that has essential roles in multiple phases of axonal...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436838/ https://www.ncbi.nlm.nih.gov/pubmed/25808489 http://dx.doi.org/10.1091/mbc.E15-01-0039 |
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author | Umeda, Kentaro Iwasawa, Nariaki Negishi, Manabu Oinuma, Izumi |
author_facet | Umeda, Kentaro Iwasawa, Nariaki Negishi, Manabu Oinuma, Izumi |
author_sort | Umeda, Kentaro |
collection | PubMed |
description | Precise wiring patterns of axons are among the remarkable features of neuronal circuit formation, and establishment of the proper neuronal network requires control of outgrowth, branching, and guidance of axons. R-Ras is a Ras-family small GTPase that has essential roles in multiple phases of axonal development. We recently identified afadin, an F-actin–binding protein, as an effector of R-Ras mediating axon branching through F-actin reorganization. Afadin comprises two isoforms—l-afadin, having the F-actin–binding domain, and s-afadin, lacking the F-actin–binding domain. Compared with l-afadin, s-afadin, the short splicing variant of l-afadin, contains RA domains but lacks the F-actin–binding domain. Neurons express both isoforms; however, the function of s-afadin in brain remains unknown. Here we identify s-afadin as an endogenous inhibitor of cortical axon branching. In contrast to the abundant and constant expression of l-afadin throughout neuronal development, the expression of s-afadin is relatively low when cortical axons branch actively. Ectopic expression and knockdown of s-afadin suppress and promote branching, respectively. s-Afadin blocks the R-Ras–mediated membrane translocation of l-afadin and axon branching by inhibiting the binding of l-afadin to R-Ras. Thus s-afadin acts as a dominant-negative isoform in R-Ras-afadin–regulated axon branching. |
format | Online Article Text |
id | pubmed-4436838 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-44368382015-07-30 A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner Umeda, Kentaro Iwasawa, Nariaki Negishi, Manabu Oinuma, Izumi Mol Biol Cell Articles Precise wiring patterns of axons are among the remarkable features of neuronal circuit formation, and establishment of the proper neuronal network requires control of outgrowth, branching, and guidance of axons. R-Ras is a Ras-family small GTPase that has essential roles in multiple phases of axonal development. We recently identified afadin, an F-actin–binding protein, as an effector of R-Ras mediating axon branching through F-actin reorganization. Afadin comprises two isoforms—l-afadin, having the F-actin–binding domain, and s-afadin, lacking the F-actin–binding domain. Compared with l-afadin, s-afadin, the short splicing variant of l-afadin, contains RA domains but lacks the F-actin–binding domain. Neurons express both isoforms; however, the function of s-afadin in brain remains unknown. Here we identify s-afadin as an endogenous inhibitor of cortical axon branching. In contrast to the abundant and constant expression of l-afadin throughout neuronal development, the expression of s-afadin is relatively low when cortical axons branch actively. Ectopic expression and knockdown of s-afadin suppress and promote branching, respectively. s-Afadin blocks the R-Ras–mediated membrane translocation of l-afadin and axon branching by inhibiting the binding of l-afadin to R-Ras. Thus s-afadin acts as a dominant-negative isoform in R-Ras-afadin–regulated axon branching. The American Society for Cell Biology 2015-05-15 /pmc/articles/PMC4436838/ /pubmed/25808489 http://dx.doi.org/10.1091/mbc.E15-01-0039 Text en © 2015 Umeda et al. 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 Umeda, Kentaro Iwasawa, Nariaki Negishi, Manabu Oinuma, Izumi A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title | A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title_full | A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title_fullStr | A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title_full_unstemmed | A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title_short | A short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
title_sort | short splicing isoform of afadin suppresses the cortical axon branching in a dominant-negative manner |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4436838/ https://www.ncbi.nlm.nih.gov/pubmed/25808489 http://dx.doi.org/10.1091/mbc.E15-01-0039 |
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