Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation.
Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kina...
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| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2012-01-01
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| Series: | PLoS Biology |
| Online Access: | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001439&type=printable |
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| _version_ | 1850190107448967168 |
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| author | Daniel Feltrin Ludovico Fusco Harald Witte Francesca Moretti Katrin Martin Michel Letzelter Erika Fluri Peter Scheiffele Olivier Pertz |
| author_facet | Daniel Feltrin Ludovico Fusco Harald Witte Francesca Moretti Katrin Martin Michel Letzelter Erika Fluri Peter Scheiffele Olivier Pertz |
| author_sort | Daniel Feltrin |
| collection | DOAJ |
| description | Local mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation. |
| format | Article |
| id | doaj-art-e0f85f53c3be48a79bd2cb15430d2472 |
| institution | OA Journals |
| issn | 1544-9173 1545-7885 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS Biology |
| spelling | doaj-art-e0f85f53c3be48a79bd2cb15430d24722025-08-20T02:15:24ZengPublic Library of Science (PLoS)PLoS Biology1544-91731545-78852012-01-011012e100143910.1371/journal.pbio.1001439Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation.Daniel FeltrinLudovico FuscoHarald WitteFrancesca MorettiKatrin MartinMichel LetzelterErika FluriPeter ScheiffeleOlivier PertzLocal mRNA translation in neurons has been mostly studied during axon guidance and synapse formation but not during initial neurite outgrowth. We performed a genome-wide screen for neurite-enriched mRNAs and identified an mRNA that encodes mitogen-activated protein kinase kinase 7 (MKK7), a MAP kinase kinase (MAPKK) for Jun kinase (JNK). We show that MKK7 mRNA localizes to the growth cone where it has the potential to be translated. MKK7 is then specifically phosphorylated in the neurite shaft, where it is part of a MAP kinase signaling module consisting of dual leucine zipper kinase (DLK), MKK7, and JNK1. This triggers Map1b phosphorylation to regulate microtubule bundling leading to neurite elongation. We propose a model in which MKK7 mRNA localization and translation in the growth cone allows for a mechanism to position JNK signaling in the neurite shaft and to specifically link it to regulation of microtubule bundling. At the same time, this uncouples activated JNK from its functions relevant to nuclear translocation and transcriptional activation.https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001439&type=printable |
| spellingShingle | Daniel Feltrin Ludovico Fusco Harald Witte Francesca Moretti Katrin Martin Michel Letzelter Erika Fluri Peter Scheiffele Olivier Pertz Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. PLoS Biology |
| title | Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. |
| title_full | Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. |
| title_fullStr | Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. |
| title_full_unstemmed | Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. |
| title_short | Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. |
| title_sort | growth cone mkk7 mrna targeting regulates map1b dependent microtubule bundling to control neurite elongation |
| url | https://journals.plos.org/plosbiology/article/file?id=10.1371/journal.pbio.1001439&type=printable |
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