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Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology

Dendritic arborization is a critical neuronal differentiation process. Here, we demonstrate that syndecan-2 (Sdc2), a synaptic heparan sulfate proteoglycan that triggers dendritic filopodia and spine formation, regulates dendritic arborization in cultured hippocampal neurons. This process is control...

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Autores principales: Chen, Chiung-Ya, Lin, Chia-Wen, Chang, Chiung-Ying, Jiang, Si-Tse, Hsueh, Yi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166868/
https://www.ncbi.nlm.nih.gov/pubmed/21555464
http://dx.doi.org/10.1083/jcb.201008050
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author Chen, Chiung-Ya
Lin, Chia-Wen
Chang, Chiung-Ying
Jiang, Si-Tse
Hsueh, Yi-Ping
author_facet Chen, Chiung-Ya
Lin, Chia-Wen
Chang, Chiung-Ying
Jiang, Si-Tse
Hsueh, Yi-Ping
author_sort Chen, Chiung-Ya
collection PubMed
description Dendritic arborization is a critical neuronal differentiation process. Here, we demonstrate that syndecan-2 (Sdc2), a synaptic heparan sulfate proteoglycan that triggers dendritic filopodia and spine formation, regulates dendritic arborization in cultured hippocampal neurons. This process is controlled by sterile α and TIR motif–containing 1 protein (Sarm1), a negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling. We show that Sarm1 interacts with and receives signal from Sdc2 and controls dendritic arborization through the MKK4–JNK pathway. In Sarm1 knockdown mice, dendritic arbors of neurons were less complex than those of wild-type littermates. In addition to acting downstream of Sdc2, Sarm1 is expressed earlier than Sdc2, which suggests that it has multiple roles in neuronal morphogenesis. Specifically, it is required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization. These functions likely involve Sarm1-mediated regulation of microtubule stability, as Sarm1 influenced tubulin acetylation. This study thus reveals the molecular mechanism underlying the action of Sarm1 in neuronal morphogenesis.
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spelling pubmed-31668682011-11-16 Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology Chen, Chiung-Ya Lin, Chia-Wen Chang, Chiung-Ying Jiang, Si-Tse Hsueh, Yi-Ping J Cell Biol Research Articles Dendritic arborization is a critical neuronal differentiation process. Here, we demonstrate that syndecan-2 (Sdc2), a synaptic heparan sulfate proteoglycan that triggers dendritic filopodia and spine formation, regulates dendritic arborization in cultured hippocampal neurons. This process is controlled by sterile α and TIR motif–containing 1 protein (Sarm1), a negative regulator of Toll-like receptor 3 (TLR3) in innate immunity signaling. We show that Sarm1 interacts with and receives signal from Sdc2 and controls dendritic arborization through the MKK4–JNK pathway. In Sarm1 knockdown mice, dendritic arbors of neurons were less complex than those of wild-type littermates. In addition to acting downstream of Sdc2, Sarm1 is expressed earlier than Sdc2, which suggests that it has multiple roles in neuronal morphogenesis. Specifically, it is required for proper initiation and elongation of dendrites, axonal outgrowth, and neuronal polarization. These functions likely involve Sarm1-mediated regulation of microtubule stability, as Sarm1 influenced tubulin acetylation. This study thus reveals the molecular mechanism underlying the action of Sarm1 in neuronal morphogenesis. The Rockefeller University Press 2011-05-16 /pmc/articles/PMC3166868/ /pubmed/21555464 http://dx.doi.org/10.1083/jcb.201008050 Text en © 2011 Chen 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
Chen, Chiung-Ya
Lin, Chia-Wen
Chang, Chiung-Ying
Jiang, Si-Tse
Hsueh, Yi-Ping
Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title_full Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title_fullStr Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title_full_unstemmed Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title_short Sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
title_sort sarm1, a negative regulator of innate immunity, interacts with syndecan-2 and regulates neuronal morphology
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3166868/
https://www.ncbi.nlm.nih.gov/pubmed/21555464
http://dx.doi.org/10.1083/jcb.201008050
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