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神经营养因子和Toll蛋白对细胞数量可塑性的三层调节作用 于…… （原句不完整，翻译只能到这里）

Three-tier regulation of cell number plasticity by neurotrophins and Tolls in .

作者信息

Foldi Istvan, Anthoney Niki, Harrison Neale, Gangloff Monique, Verstak Brett, Nallasivan Mohanakarthik Ponnadai, AlAhmed Samaher, Zhu Bangfu, Phizacklea Mark, Losada-Perez Maria, Moreira Marta, Gay Nicholas J, Hidalgo Alicia

机构信息

NeuroDevelopment Group, School of Biosciences, University of Birmingham, Birmingham B15 2TT, England, UK.

Department of Biochemistry, University of Cambridge, Cambridge CB2 1GA, England, UK.

出版信息

J Cell Biol. 2017 May 1;216(5):1421-1438. doi: 10.1083/jcb.201607098. Epub 2017 Apr 3.

DOI:10.1083/jcb.201607098
PMID:28373203
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5412559/
Abstract

Cell number plasticity is coupled to circuitry in the nervous system, adjusting cell mass to functional requirements. In mammals, this is achieved by neurotrophin (NT) ligands, which promote cell survival via their Trk and p75 receptors and cell death via p75 and Sortilin. NTs (DNTs) bind Toll receptors instead to promote neuronal survival, but whether they can also regulate cell death is unknown. In this study, we show that DNTs and Tolls can switch from promoting cell survival to death in the central nervous system (CNS) via a three-tier mechanism. First, DNT cleavage patterns result in alternative signaling outcomes. Second, different Tolls can preferentially promote cell survival or death. Third, distinct adaptors downstream of Tolls can drive either apoptosis or cell survival. Toll-6 promotes cell survival via MyD88-NF-κB and cell death via Wek-Sarm-JNK. The distribution of adaptors changes in space and time and may segregate to distinct neural circuits. This novel mechanism for CNS cell plasticity may operate in wider contexts.

摘要

细胞数量可塑性与神经系统中的神经回路相关联，可根据功能需求调节细胞数量。在哺乳动物中，这是通过神经营养因子（NT）配体实现的，它们通过Trk和p75受体促进细胞存活，并通过p75和Sortilin促进细胞死亡。而双功能神经营养因子（DNTs）则结合Toll受体来促进神经元存活，但它们是否也能调节细胞死亡尚不清楚。在本研究中，我们表明DNTs和Toll受体可通过一种三层机制在中枢神经系统（CNS）中从促进细胞存活转变为促进细胞死亡。首先，DNT的切割模式导致不同的信号转导结果。其次，不同的Toll受体可优先促进细胞存活或死亡。第三，Toll受体下游不同的衔接蛋白可驱动细胞凋亡或细胞存活。Toll-6通过MyD88-NF-κB促进细胞存活，并通过Wek-Sarm-JNK促进细胞死亡。衔接蛋白的分布在空间和时间上发生变化，并可能分隔到不同的神经回路中。这种中枢神经系统细胞可塑性的新机制可能在更广泛的背景下起作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/f4fcba2e2c40/JCB_201607098_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/964b39b31a65/JCB_201607098_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/20653129729e/JCB_201607098_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/81d665426dc9/JCB_201607098_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/d897bf0289d7/JCB_201607098_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/35987af7dcee/JCB_201607098_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/152439b7eb4a/JCB_201607098_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/4b5996852b7c/JCB_201607098_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/f4fcba2e2c40/JCB_201607098_Fig8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/964b39b31a65/JCB_201607098_Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/20653129729e/JCB_201607098_Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/81d665426dc9/JCB_201607098_Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/d897bf0289d7/JCB_201607098_Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/35987af7dcee/JCB_201607098_Fig5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/152439b7eb4a/JCB_201607098_Fig6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/4b5996852b7c/JCB_201607098_Fig7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/329f/5412559/f4fcba2e2c40/JCB_201607098_Fig8.jpg

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