Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila.
Three-tier regulation of cell number plasticity by neurotrophins and Tolls in Drosophila.
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DOI：
10.1083/jcb.201607098
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发表时间：
2017-05-01
期刊：
影响因子：
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通讯作者：
Hidalgo A
中科院分区：
文献类型：
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作者：
Foldi I;Anthoney N;Harrison N;Gangloff M;Verstak B;Nallasivan MP;AlAhmed S;Zhu B;Phizacklea M;Losada-Perez M;Moreira M;Gay NJ;Hidalgo A
涉及不同神经营养因子家族配体形式、不同Toll受体和不同衔接子的三层机制调节细胞存活和死亡。这种丰富的机制赋予细胞数量可塑性，并可能成为神经系统结构可塑性和更广泛背景下的结构完整性，稳态和再生的基础。细胞数量的可塑性与神经系统中的回路相关联，调节细胞质量以满足功能需求。在哺乳动物中，这是通过神经营养因子（NT）配体实现的，其通过Trk和p75 NTR受体促进细胞存活，并通过p75 NTR和分拣蛋白促进细胞死亡。果蝇NTs（DNT）结合Toll受体，以促进神经元的存活，但它们是否也能调节细胞死亡尚不清楚。在这项研究中，我们表明DNT和Toll可以通过三层机制在中枢神经系统（CNS）中从促进细胞存活转变为死亡。首先，DNT切割模式导致替代信号传导结果。第二，不同的Toll可以优先促进细胞存活或死亡。第三，Toll下游的不同衔接子可以驱动细胞凋亡或细胞存活。Toll-6通过MyD 88-NF-κB促进细胞存活，通过Wek-Sarm-JNK促进细胞死亡。适配器的分布在空间和时间上发生变化，并可能分离到不同的神经回路。CNS细胞可塑性的这种新机制可能在更广泛的背景下起作用。
A three-tier mechanism involving distinct neurotrophin family ligand forms, different Toll receptors, and different adaptors regulates both cell survival and death. This rich mechanism confers cell number plasticity and could underlie structural plasticity in the nervous system and structural integrity, homeostasis, and regeneration in wider contexts. 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 p75NTR receptors and cell death via p75NTR and Sortilin. Drosophila 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.