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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...

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Detalles Bibliográficos
Autores principales: Ballard, Shannon L., Miller, Daniel L., Ganetzky, Barry
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2014
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.
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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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