Nmnat exerts neuroprotective effects in dendrites and axons.
Nmnat exerts neuroprotective effects in dendrites and axons.
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DOI：
10.1016/j.mcn.2011.05.002
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发表时间：
2011-09
影响因子：
3.5
通讯作者：
Kim, Michael D.
中科院分区：
文献类型：
--
作者：
Wen, Yuhui;Parrish, Jay Z.;He, Ruina;Zhai, R. Grace;Kim, Michael D.
树突在最初建立接受野的覆盖范围后，可以维持较长时间。树突的长期维持是突触连通性的基础，但神经元如何在整个发育过程中建立并维持其树突树突模式尚不清楚。在这里，我们表明NAD合成酶烟酰胺单核苷酸腺苷转移酶（Nmnat）是维持果蝇树突树突（da）感觉神经元类型特异性树突覆盖所必需的细胞自主。在nmnat杂合突变体中，IV类da神经元的树突树突模式在后期发育阶段，在末端分支的收缩增加和生长减少导致树突覆盖的进行性缺陷之前被适当地建立。尽管感觉轴突在nmnat杂合子中基本完整，但nmnat功能的完全丧失会导致严重的轴突变性，这表明在维持树突树突模式和轴突完整性方面，nmnat剂量的要求不同。Nmnat的过表达可以抑制与肿瘤抑制激酶疣（Wts）缺失相关的树突维持缺陷，这证明Nmnat除了在轴突中具有神经保护作用外，还可以作为防止进行性树突缺失的保护因子。此外，缺乏nmnat的运动神经元在树突和轴突都表现出进行性缺陷。我们的研究揭示了内源性Nmnat在维持轴突和树突完整性方面的重要作用，并提供了Nmnat在中枢神经系统中广泛的神经保护作用的证据。
Dendrites can be maintained for extended periods of time after they initially establish coverage of their receptive field. The long-term maintenance of dendrites underlies synaptic connectivity, but how neurons establish and then maintain their dendritic arborization patterns throughout development is not well understood. Here, we show that the NAD synthase Nicotinamide mononucleotide adenylyltransferase (Nmnat) is cell-autonomously required for maintaining type-specific dendritic coverage of Drosophila dendritic arborization (da) sensory neurons. In nmnat heterozygous mutants, dendritic arborization patterns of class IV da neurons are properly established before increased retraction and decreased growth of terminal branches lead to progressive defects in dendritic coverage during later stages of development. Although sensory axons are largely intact in nmnat heterozygotes, complete loss of nmnat function causes severe axonal degeneration, demonstrating differential requirements for nmnat dosage in the maintenance of dendritic arborization patterns and axonal integrity. Overexpression of Nmnat suppresses dendrite maintenance defects associated with loss of the tumor suppressor kinase Warts (Wts), providing evidence that Nmnat, in addition to its neuroprotective role in axons, can function as a protective factor against progressive dendritic loss. Moreover, motor neurons deficient for nmnat show progressive defects in both dendrites and axons. Our studies reveal an essential role for endogenous Nmnat function in the maintenance of both axonal and dendritic integrity and present evidence of a broad neuroprotective role for Nmnat in the central nervous system.
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影响因子：
5.3
作者：
Fischer, LR;Culver, DG;Glass, JD
通讯作者：
Glass, JD
影响因子：
25
作者：
Mack, TGA;Reiner, M;Coleman, MP
通讯作者：
Coleman, MP
影响因子：
2.5
作者：
CERF, JA;CHACKO, LW
通讯作者：
CHACKO, LW
DOI：
10.1523/jneurosci.5469-08.2009
发表时间：
2009-04-29
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Sasaki Y;Vohra BP;Lund FE;Milbrandt J
通讯作者：
Milbrandt J
DOI：
10.1083/jcb.200808042
发表时间：
2009-02-23
期刊：
The Journal of cell biology
影响因子：
--
作者：
Avery MA;Sheehan AE;Kerr KS;Wang J;Freeman MR
通讯作者：
Freeman MR