UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.
UNC79 and UNC80, putative auxiliary subunits of the NARROW ABDOMEN ion channel, are indispensable for robust circadian locomotor rhythms in Drosophila.
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DOI：
10.1371/journal.pone.0078147
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Allada R
中科院分区：
文献类型：
--
作者：
Lear BC;Darrah EJ;Aldrich BT;Gebre S;Scott RL;Nash HA;Allada R
在果蝇黑腹果蝇中，一个昼夜节律起搏器神经元网络驱动着日常休息和活动的节奏。窄腹离子通道（NA）与哺乳动物钠泄漏通道NALCN同源，在起搏器神经元分子生物钟的下游起作用，促进行为节律性。为了更好地理解NA通道的功能和调控，我们对果蝇中两个可能的辅助通道亚基unc79（又名dunc79）和unc80（又名CG18437）进行了表征。我们已经产生了新的unc79和unc80突变，它们代表了强或完全丧失功能的等位基因。这些突变体在昼夜运动节律性方面表现出严重的缺陷，与na突变表型难以区分。组织特异性RNA干扰和抢救分析表明，UNC79和UNC80可能在起搏器神经元中起作用，与NA具有相似的解剖要求。我们观察到这三种基因产物之间存在相互依赖的转录后调控关系，因为na、unc79或unc80基因功能的缺失会导致这三种蛋白的表达减少，而对转录水平的影响很小。然而，尽管存在这种关系，我们发现在昼夜节律中对unc79和unc80的需求不能通过增加NA蛋白表达来绕过，这些假定的辅助亚基也不能相互替代。这些数据表明，除了促进通道亚基表达外，UNC79和UNC80的功能需求。免疫沉淀实验也证实了在果蝇大脑中UNC79和UNC80与NA形成复合物。综上所述，这些数据表明果蝇NA、UNC79和UNC80在生物钟神经元中共同起作用，促进有节奏的行为。
In the fruit fly Drosophila melanogaster, a network of circadian pacemaker neurons drives daily rhythms in rest and activity. The ion channel NARROW ABDOMEN (NA), orthologous to the mammalian sodium leak channel NALCN, functions downstream of the molecular circadian clock in pacemaker neurons to promote behavioral rhythmicity. To better understand the function and regulation of the NA channel, we have characterized two putative auxiliary channel subunits in Drosophila, unc79 (aka dunc79) and unc80 (aka CG18437). We have generated novel unc79 and unc80 mutations that represent strong or complete loss-of-function alleles. These mutants display severe defects in circadian locomotor rhythmicity that are indistinguishable from na mutant phenotypes. Tissue-specific RNA interference and rescue analyses indicate that UNC79 and UNC80 likely function within pacemaker neurons, with similar anatomical requirements to NA. We observe an interdependent, post-transcriptional regulatory relationship among the three gene products, as loss of na, unc79, or unc80 gene function leads to decreased expression of all three proteins, with minimal effect on transcript levels. Yet despite this relationship, we find that the requirement for unc79 and unc80 in circadian rhythmicity cannot be bypassed by increasing NA protein expression, nor can these putative auxiliary subunits substitute for each other. These data indicate functional requirements for UNC79 and UNC80 beyond promoting channel subunit expression. Immunoprecipitation experiments also confirm that UNC79 and UNC80 form a complex with NA in the Drosophila brain. Taken together, these data suggest that Drosophila NA, UNC79, and UNC80 function together in circadian clock neurons to promote rhythmic behavior.
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影响因子：
12.3
作者：
Cook RK;Christensen SJ;Deal JA;Coburn RA;Deal ME;Gresens JM;Kaufman TC;Cook KR
通讯作者：
Cook KR
影响因子：
9.2
作者：
Humphrey, John A.;Hamming, Kevin S.;Nash, Howard A.
通讯作者：
Nash, Howard A.
影响因子：
2.5
作者：
LeSauter, Joseph;Silver, Rae;Witkovsky, Paul
通讯作者：
Witkovsky, Paul
肽神经递质激活 NALCN 和 UNC-80 的阳离子通道复合物。
影响因子：
64.8
作者：
Lu, Boxun;Su, Yanhua;Das, Sudipto;Wang, Haikun;Wang, Yan;Liu, Jin;Ren, Dejian
通讯作者：
Ren, Dejian
影响因子：
18.2
作者：
Allada R;Chung BY
通讯作者：
Chung BY