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Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation
In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655820/ https://www.ncbi.nlm.nih.gov/pubmed/23536706 http://dx.doi.org/10.1091/mbc.E12-11-0782 |
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author | Ueda, Shuhei Negishi, Manabu Katoh, Hironori |
author_facet | Ueda, Shuhei Negishi, Manabu Katoh, Hironori |
author_sort | Ueda, Shuhei |
collection | PubMed |
description | In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)–mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac. |
format | Online Article Text |
id | pubmed-3655820 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-36558202013-07-30 Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation Ueda, Shuhei Negishi, Manabu Katoh, Hironori Mol Biol Cell Articles In neuronal development, dendritic spine formation is important for the establishment of excitatory synaptic connectivity and functional neural circuits. Developmental deficiency in spine formation results in multiple neuropsychiatric disorders. Dock4, a guanine nucleotide exchange factor (GEF) for Rac, has been reported as a candidate genetic risk factor for autism, dyslexia, and schizophrenia. We previously showed that Dock4 is expressed in hippocampal neurons. However, the functions of Dock4 in hippocampal neurons and the underlying molecular mechanisms are poorly understood. Here we show that Dock4 is highly concentrated in dendritic spines and implicated in spine formation via interaction with the actin-binding protein cortactin. In cultured neurons, short hairpin RNA (shRNA)–mediated knockdown of Dock4 reduces dendritic spine density, which is rescued by coexpression of shRNA-resistant wild-type Dock4 but not by a GEF-deficient mutant of Dock4 or a truncated mutant lacking the cortactin-binding region. On the other hand, knockdown of cortactin suppresses Dock4-mediated spine formation. Taken together, the results show a novel and functionally important interaction between Dock4 and cortactin for regulating dendritic spine formation via activation of Rac. The American Society for Cell Biology 2013-05-15 /pmc/articles/PMC3655820/ /pubmed/23536706 http://dx.doi.org/10.1091/mbc.E12-11-0782 Text en © 2013 Ueda 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 of Cell BD; are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Ueda, Shuhei Negishi, Manabu Katoh, Hironori Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title | Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title_full | Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title_fullStr | Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title_full_unstemmed | Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title_short | Rac GEF Dock4 interacts with cortactin to regulate dendritic spine formation |
title_sort | rac gef dock4 interacts with cortactin to regulate dendritic spine formation |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3655820/ https://www.ncbi.nlm.nih.gov/pubmed/23536706 http://dx.doi.org/10.1091/mbc.E12-11-0782 |
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