Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.
Loss of Na(+)/K(+)-ATPase in Drosophila photoreceptors leads to blindness and age-dependent neurodegeneration.
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DOI：
10.1016/j.expneurol.2014.08.025
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发表时间：
2014-11
影响因子：
5.3
通讯作者：
Li, Hong-Sheng
中科院分区：
文献类型：
--
作者：
Luan, Zhuo;Reddig, Keith;Li, Hong-Sheng
The activity of Na+/K+-ATPase establishes transmembrane ion gradients and is essential to cell function and survival. Either dysregulation or deficiency of neuronal Na+/K+-ATPase has been implicated in the pathogenesis of many neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and rapid-onset dystonia Parkinsonism. However, genetic evidence that directly links neuronal Na+/K+-ATPase deficiency to in vivo neurodegeneration has been lacking. In this study, we use Drosophila photoreceptors to investigate the cell-autonomous effects of neuronal Na+/K+ ATPase. Loss of ATPα, an α subunit of Na+/K+-ATPase, in photoreceptors through UAS/Gal4-mediated RNAi eliminated the light-triggered depolarization of the photoreceptors, rendering the fly virtually blind in behavioral assays. Intracellular recordings indicated that ATPα knockdown photoreceptors were already depolarized in the dark, which was due to a loss of intracellular K+. Importantly, ATPα knockdown resulted in the degeneration of photoreceptors in older flies. This degeneration was independent of light and showed characteristics of apoptotic/hybrid cell death as observed via electron microscopy analysis. Loss of Nrv3, a Na+/K+-ATPase β subunit, partially reproduced the signaling and degenerative defects observed in ATPα knockdown flies. Thus, loss of Na+/K+-ATPase not only eradicates visual function but also causes age-dependent degeneration in photoreceptors, confirming the link between neuronal Na+/K+ ATPase deficiency and in vivo neurodegeneration. This work also establishes Drosophila photoreceptors as a genetic model for studying the cell-autonomous mechanisms underlying neuronal Na+/K+ ATPase deficiency-mediated neurodegeneration.
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影响因子：
16.2
作者：
Kiselev, A;Socolich, M;Ranganathan, R
通讯作者：
Ranganathan, R
影响因子：
2.7
作者：
DeAndrade, Mark P.;Yokoi, Fumiaki;Li, Yuqing
通讯作者：
Li, Yuqing
DOI：
10.1111/j.1749-6632.1991.tb17294.x
发表时间：
1991-12-18
影响因子：
5.2
作者：
DIPOLO, R;BEAUGE, L
通讯作者：
BEAUGE, L
影响因子：
2.9
作者：
Keep, RF;Ulanski, LJ;Betz, AL
通讯作者：
Betz, AL
DOI：
10.1083/jcb.110.1.165
发表时间：
1990-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Gloor S;Antonicek H;Sweadner KJ;Pagliusi S;Frank R;Moos M;Schachner M
通讯作者：
Schachner M