The role of autophagy in Nmnat-mediated protection against hypoxia-induced dendrite degeneration.
The role of autophagy in Nmnat-mediated protection against hypoxia-induced dendrite degeneration.
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DOI：
10.1016/j.mcn.2012.11.008
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发表时间：
2013-01
期刊：
影响因子：
--
通讯作者：
Kim MD
中科院分区：
文献类型：
--
作者：
Wen Y;Zhai RG;Kim MD
The selective degeneration of dendrites precedes neuronal cell death in hypoxia-ischemia (HI) and is a neuropathological hallmark of stroke. While it is clear that a number of different molecular pathways likely contribute to neuronal cell death in HI, the mechanisms that govern HI-induced dendrite degeneration are largely unknown. Here, we show that the NAD synthase Nicotinamide mononucleotide adenylyltransferase (Nmnat) functions endogenously to protect Drosophila class IV dendritic arborization (da) sensory neurons against hypoxia-induced dendritic damage. Whereas dendrites of wild-type class IV neurons are largely resistant to morphological changes during prolonged periods of hypoxia (< 1.0% O2), class IV neurons of nmnat heterozygous mutants exhibit significant dendrite loss and extensive fragmentation of the dendritic arbor under the same hypoxic conditions. Although basal levels of autophagy are required for neuronal survival, we demonstrate that autophagy is dispensable for maintaining the dendritic integrity of class IV neurons. However, we find that genetically blocking autophagy can suppress hypoxia-induced dendrite degeneration of nmnat heterozygous mutants in a cell-autonomous manner, suggestive of a self-destructive role for autophagy in this context. We further show that inducing autophagy by overexpression of the autophagy-specific kinase Atg1 is sufficient to cause dendrite degeneration of class IV neurons under hypoxia and that overexpression of Nmnat fails to protect class IV dendrites from the effects of Atg1 overexpression. Our studies reveal an essential neuroprotective role for endogenous Nmnat in hypoxia and demonstrate that Nmnat functions upstream of autophagy to mitigate the damage incurred by dendrites in neurons under hypoxic stress.
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影响因子：
5.3
作者：
Hu, BR;Martone, ME;Liu, CL
通讯作者：
Liu, CL
DOI：
10.1186/1478-811x-10-7
发表时间：
2012-03-13
期刊：
Cell communication and signaling : CCS
影响因子：
--
作者：
Alers S;Löffler AS;Wesselborg S;Stork B
通讯作者：
Stork B
影响因子：
16.2
作者：
Han C;Wang D;Soba P;Zhu S;Lin X;Jan LY;Jan YN
通讯作者：
Jan YN
影响因子：
6.1
作者：
Carloni, Silvia;Buonocore, Giuseppe;Balduini, Walter
通讯作者：
Balduini, Walter
影响因子：
4
作者：
Chen, Yongqiang;Klionsky, Daniel J.
通讯作者：
Klionsky, Daniel J.