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Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila
Toll-like receptors (TLRs) are best characterized for their roles in mediating dorsoventral patterning and the innate immune response. However, recent studies indicate that TLRs are also involved in regulating neuronal growth and development. Here, we demonstrate that the TLR Tollo positively regula...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Rockefeller University Press
2014
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971753/ https://www.ncbi.nlm.nih.gov/pubmed/24662564 http://dx.doi.org/10.1083/jcb.201308115 |
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author | Ballard, Shannon L. Miller, Daniel L. Ganetzky, Barry |
author_facet | Ballard, Shannon L. Miller, Daniel L. Ganetzky, Barry |
author_sort | Ballard, Shannon L. |
collection | PubMed |
description | Toll-like receptors (TLRs) are best characterized for their roles in mediating dorsoventral patterning and the innate immune response. However, recent studies indicate that TLRs are also involved in regulating neuronal growth and development. Here, we demonstrate that the TLR Tollo positively regulates growth of the Drosophila melanogaster larval neuromuscular junction (NMJ). Tollo mutants exhibited NMJ undergrowth, whereas increased expression of Tollo led to NMJ overgrowth. Tollo expression in the motoneuron was both necessary and sufficient for regulating NMJ growth. Dominant genetic interactions together with altered levels of phosphorylated c-Jun N-terminal kinase (JNK) and puc-lacZ expression revealed that Tollo signals through the JNK pathway at the NMJ. Genetic interactions also revealed that the neurotrophin Spätzle3 (Spz3) is a likely Tollo ligand. Spz3 expression in muscle and proteolytic activation via the Easter protease was necessary and sufficient to promote NMJ growth. These results demonstrate the existence of a novel neurotrophin signaling pathway that is required for synaptic development in Drosophila. |
format | Online Article Text |
id | pubmed-3971753 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-39717532014-10-01 Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila Ballard, Shannon L. Miller, Daniel L. Ganetzky, Barry J Cell Biol Research Articles Toll-like receptors (TLRs) are best characterized for their roles in mediating dorsoventral patterning and the innate immune response. However, recent studies indicate that TLRs are also involved in regulating neuronal growth and development. Here, we demonstrate that the TLR Tollo positively regulates growth of the Drosophila melanogaster larval neuromuscular junction (NMJ). Tollo mutants exhibited NMJ undergrowth, whereas increased expression of Tollo led to NMJ overgrowth. Tollo expression in the motoneuron was both necessary and sufficient for regulating NMJ growth. Dominant genetic interactions together with altered levels of phosphorylated c-Jun N-terminal kinase (JNK) and puc-lacZ expression revealed that Tollo signals through the JNK pathway at the NMJ. Genetic interactions also revealed that the neurotrophin Spätzle3 (Spz3) is a likely Tollo ligand. Spz3 expression in muscle and proteolytic activation via the Easter protease was necessary and sufficient to promote NMJ growth. These results demonstrate the existence of a novel neurotrophin signaling pathway that is required for synaptic development in Drosophila. The Rockefeller University Press 2014-03-31 /pmc/articles/PMC3971753/ /pubmed/24662564 http://dx.doi.org/10.1083/jcb.201308115 Text en © 2014 Ballard et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/). |
spellingShingle | Research Articles Ballard, Shannon L. Miller, Daniel L. Ganetzky, Barry Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title | Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title_full | Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title_fullStr | Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title_full_unstemmed | Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title_short | Retrograde neurotrophin signaling through Tollo regulates synaptic growth in Drosophila |
title_sort | retrograde neurotrophin signaling through tollo regulates synaptic growth in drosophila |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3971753/ https://www.ncbi.nlm.nih.gov/pubmed/24662564 http://dx.doi.org/10.1083/jcb.201308115 |
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