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Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A
Fragile X syndrome, the most frequent form of familial mental retardation, is caused by mutation of the Fmr1 gene. Fmr1 encodes the fragile X mental retardation protein (FMRP), an mRNA binding protein regulating local, postsynaptic mRNA translation along dendrites necessary for long-term synaptic pl...
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Formato: | Texto |
Lenguaje: | English |
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Frontiers Research Foundation
2009
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759364/ https://www.ncbi.nlm.nih.gov/pubmed/19826618 http://dx.doi.org/10.3389/neuro.04.011.2009 |
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author | Li, Chanxia Bassell, Gary J. Sasaki, Yukio |
author_facet | Li, Chanxia Bassell, Gary J. Sasaki, Yukio |
author_sort | Li, Chanxia |
collection | PubMed |
description | Fragile X syndrome, the most frequent form of familial mental retardation, is caused by mutation of the Fmr1 gene. Fmr1 encodes the fragile X mental retardation protein (FMRP), an mRNA binding protein regulating local, postsynaptic mRNA translation along dendrites necessary for long-term synaptic plasticity. However, recent studies on FMRP localization in axons and growth cones suggest a possible function in the regulation of local protein synthesis needed for axon guidance. Here, we have demonstrated that FMRP is involved in axonal and growth cone responses induced by the axon guidance factor, Semaphorin-3A (Sema3A). In cultured hippocampal neurons from wild type mice, Sema3A-induced growth cone collapse was protein synthesis-dependent. In contrast, Sema3A-induced growth cone collapse was attenuated in Fmr1 knock-out (KO) neurons and insensitive to protein synthesis inhibitors, suggesting that FMRP is involved in protein synthesis-dependent growth cone collapse. Sema3A increased phosphorylation of eukaryotic initiation factor 4E (eIF4E), an indicator of local translation, in distal axons and growth cones of wild type, but not Fmr1 KO neurons. Furthermore, Sema3A rapidly induced a protein synthesis-dependent increase in levels of microtubule associated protein 1B (MAP1B) in distal axons of wild type neurons, but this response was attenuated in Fmr1 KO neurons. These results suggest a possible role of FMRP to regulate local translation and axonal protein localization in response to Sema3A. This study reveals a new link between FMRP and semaphorin signaling in vitro, and raises the possibility that FMRP may have a critical role in semaphorin signaling in axon guidance during brain development. |
format | Text |
id | pubmed-2759364 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Frontiers Research Foundation |
record_format | MEDLINE/PubMed |
spelling | pubmed-27593642009-10-13 Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A Li, Chanxia Bassell, Gary J. Sasaki, Yukio Front Neural Circuits Neuroscience Fragile X syndrome, the most frequent form of familial mental retardation, is caused by mutation of the Fmr1 gene. Fmr1 encodes the fragile X mental retardation protein (FMRP), an mRNA binding protein regulating local, postsynaptic mRNA translation along dendrites necessary for long-term synaptic plasticity. However, recent studies on FMRP localization in axons and growth cones suggest a possible function in the regulation of local protein synthesis needed for axon guidance. Here, we have demonstrated that FMRP is involved in axonal and growth cone responses induced by the axon guidance factor, Semaphorin-3A (Sema3A). In cultured hippocampal neurons from wild type mice, Sema3A-induced growth cone collapse was protein synthesis-dependent. In contrast, Sema3A-induced growth cone collapse was attenuated in Fmr1 knock-out (KO) neurons and insensitive to protein synthesis inhibitors, suggesting that FMRP is involved in protein synthesis-dependent growth cone collapse. Sema3A increased phosphorylation of eukaryotic initiation factor 4E (eIF4E), an indicator of local translation, in distal axons and growth cones of wild type, but not Fmr1 KO neurons. Furthermore, Sema3A rapidly induced a protein synthesis-dependent increase in levels of microtubule associated protein 1B (MAP1B) in distal axons of wild type neurons, but this response was attenuated in Fmr1 KO neurons. These results suggest a possible role of FMRP to regulate local translation and axonal protein localization in response to Sema3A. This study reveals a new link between FMRP and semaphorin signaling in vitro, and raises the possibility that FMRP may have a critical role in semaphorin signaling in axon guidance during brain development. Frontiers Research Foundation 2009-09-15 /pmc/articles/PMC2759364/ /pubmed/19826618 http://dx.doi.org/10.3389/neuro.04.011.2009 Text en Copyright © 2009 Li, Bassell and Sasaki. http://www.frontiersin.org/licenseagreement This is an open-access article subject to an exclusive license agreement between the authors and the Frontiers Research Foundation, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are credited. |
spellingShingle | Neuroscience Li, Chanxia Bassell, Gary J. Sasaki, Yukio Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title | Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title_full | Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title_fullStr | Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title_full_unstemmed | Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title_short | Fragile X Mental Retardation Protein is Involved in Protein Synthesis-Dependent Collapse of Growth Cones Induced by Semaphorin-3A |
title_sort | fragile x mental retardation protein is involved in protein synthesis-dependent collapse of growth cones induced by semaphorin-3a |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2759364/ https://www.ncbi.nlm.nih.gov/pubmed/19826618 http://dx.doi.org/10.3389/neuro.04.011.2009 |
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