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MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival

The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1–4 in host defense were demonstrated by defec...

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Detalles Bibliográficos
Autores principales: Kim, Younghwa, Zhou, Ping, Qian, Liping, Chuang, Jen-Zen, Lee, Jessica, Li, Chenjian, Iadecola, Costantino, Nathan, Carl, Ding, Aihao
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118693/
https://www.ncbi.nlm.nih.gov/pubmed/17724133
http://dx.doi.org/10.1084/jem.20070868
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author Kim, Younghwa
Zhou, Ping
Qian, Liping
Chuang, Jen-Zen
Lee, Jessica
Li, Chenjian
Iadecola, Costantino
Nathan, Carl
Ding, Aihao
author_facet Kim, Younghwa
Zhou, Ping
Qian, Liping
Chuang, Jen-Zen
Lee, Jessica
Li, Chenjian
Iadecola, Costantino
Nathan, Carl
Ding, Aihao
author_sort Kim, Younghwa
collection PubMed
description The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1–4 in host defense were demonstrated by defective immune responses in knockout mice. In contrast, the sites of expression and functions of vertebrate MyD88-5 have remained elusive. We show that MyD88-5 is distinct from other MyD88s in that MyD88-5 is preferentially expressed in neurons, colocalizes in part with mitochondria and JNK3, and regulates neuronal death. We prepared MyD88-5/GFP transgenic mice via a bacterial artificial chromosome to preserve its endogenous expression pattern. MyD88-5/GFP was detected chiefly in the brain, where it associated with punctate structures within neurons and copurified in part with mitochondria. In vitro, MyD88-5 coimmunoprecipitated with JNK3 and recruited JNK3 from cytosol to mitochondria. Hippocampal neurons from MyD88-5–deficient mice were protected from death after deprivation of oxygen and glucose. In contrast, MyD88-5–null macrophages behaved like wild-type cells in their response to microbial products. Thus, MyD88-5 appears unique among MyD88s in functioning to mediate stress-induced neuronal toxicity.
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spelling pubmed-21186932008-03-03 MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival Kim, Younghwa Zhou, Ping Qian, Liping Chuang, Jen-Zen Lee, Jessica Li, Chenjian Iadecola, Costantino Nathan, Carl Ding, Aihao J Exp Med Articles The innate immune system relies on evolutionally conserved Toll-like receptors (TLRs) to recognize diverse microbial molecular structures. Most TLRs depend on a family of adaptor proteins termed MyD88s to transduce their signals. Critical roles of MyD88-1–4 in host defense were demonstrated by defective immune responses in knockout mice. In contrast, the sites of expression and functions of vertebrate MyD88-5 have remained elusive. We show that MyD88-5 is distinct from other MyD88s in that MyD88-5 is preferentially expressed in neurons, colocalizes in part with mitochondria and JNK3, and regulates neuronal death. We prepared MyD88-5/GFP transgenic mice via a bacterial artificial chromosome to preserve its endogenous expression pattern. MyD88-5/GFP was detected chiefly in the brain, where it associated with punctate structures within neurons and copurified in part with mitochondria. In vitro, MyD88-5 coimmunoprecipitated with JNK3 and recruited JNK3 from cytosol to mitochondria. Hippocampal neurons from MyD88-5–deficient mice were protected from death after deprivation of oxygen and glucose. In contrast, MyD88-5–null macrophages behaved like wild-type cells in their response to microbial products. Thus, MyD88-5 appears unique among MyD88s in functioning to mediate stress-induced neuronal toxicity. The Rockefeller University Press 2007-09-03 /pmc/articles/PMC2118693/ /pubmed/17724133 http://dx.doi.org/10.1084/jem.20070868 Text en Copyright © 2007, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Kim, Younghwa
Zhou, Ping
Qian, Liping
Chuang, Jen-Zen
Lee, Jessica
Li, Chenjian
Iadecola, Costantino
Nathan, Carl
Ding, Aihao
MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title_full MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title_fullStr MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title_full_unstemmed MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title_short MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival
title_sort myd88-5 links mitochondria, microtubules, and jnk3 in neurons and regulates neuronal survival
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118693/
https://www.ncbi.nlm.nih.gov/pubmed/17724133
http://dx.doi.org/10.1084/jem.20070868
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