Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.
Mmp1 processing of the PDF neuropeptide regulates circadian structural plasticity of pacemaker neurons.
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DOI：
10.1371/journal.pgen.1004700
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发表时间：
2014-10
期刊：
影响因子：
4.5
通讯作者：
Ceriani MF
中科院分区：
文献类型：
--
作者：
Depetris-Chauvin A;Fernández-Gamba A;Gorostiza EA;Herrero A;Castaño EM;Ceriani MF
在果蝇脑中，神经肽色素分散因子(PDF)在小的和大的外侧腹侧神经元(LNv)中表达，并调节昼夜运动行为。有趣的是，由于sLNv投射的显著重塑，背侧终末的PDF免疫反应性随着突触接触的变化而发生变化。尽管这一现象与电路的可塑性和行为有关，但其潜在的机制仍然知之甚少。在这项工作中，我们提供的证据表明，PDF和基质金属蛋白酶(MMP1和MMP2)是控制昼夜节律结构重构的关键。成人特有的PDF水平下调本身阻碍了昼夜节律轴突重塑，就像它改变了发育后PDF神经元中的MMP1或MMP2水平一样。然而，只有MMP1影响背侧终末的PDF免疫反应，并对显性行为产生明显的影响。体外分析表明，PDF可被MMP1水解，从而提示MMP1可直接终止其生物学活性。这些数据表明，MMP1调节PDF的处理，导致日常结构重塑和昼夜行为。生物钟已经演变成一种机制，使生物体能够适应昼夜周期性的变化，这是地球自转的直接结果。在过去的二十年里，由于其令人惊叹的遗传工具库，果蝇在发现解释时钟如何在单细胞水平运行的基因方面一直处于领先地位，这些基因在整个动物界都是保守的。尽管这些分子时钟背后的生化成分已经被详细描述，但时钟神经元用来将信息传递到控制行为的下游通路的机制仍然难以捉摸。在果蝇中，被称为小腹侧神经元(SLNvS)的昼夜节律神经元的子集能够依靠一种名为色素分散因子(PDF)的神经肽来同步其他时钟细胞。此外，几年前，我们描述了另一种可能的机制，有助于sLNvS下游的信息传递，涉及这些昼夜节律神经元轴突终末的成人特异性重塑。在这份手稿中，我们描述了一些分子事件，这些事件导致了每天这种引人注目的结构可塑性。
In the Drosophila brain, the neuropeptide PIGMENT DISPERSING FACTOR (PDF) is expressed in the small and large Lateral ventral neurons (LNvs) and regulates circadian locomotor behavior. Interestingly, PDF immunoreactivity at the dorsal terminals changes across the day as synaptic contacts do as a result of a remarkable remodeling of sLNv projections. Despite the relevance of this phenomenon to circuit plasticity and behavior, the underlying mechanisms remain poorly understood. In this work we provide evidence that PDF along with matrix metalloproteinases (Mmp1 and 2) are key in the control of circadian structural remodeling. Adult-specific downregulation of PDF levels per se hampers circadian axonal remodeling, as it does altering Mmp1 or Mmp2 levels within PDF neurons post-developmentally. However, only Mmp1 affects PDF immunoreactivity at the dorsal terminals and exerts a clear effect on overt behavior. In vitro analysis demonstrated that PDF is hydrolyzed by Mmp1, thereby suggesting that Mmp1 could directly terminate its biological activity. These data demonstrate that Mmp1 modulates PDF processing, which leads to daily structural remodeling and circadian behavior. Circadian clocks have evolved as mechanisms that allow organisms to adapt to the day/night cyclical changes, a direct consequence of the rotation of the Earth. In the last two decades, and due to its amazing repertoire of genetic tools, Drosophila has been at the leading front in the discovery of genes that account for how the clock operates at a single cell level, which are conserved throughout the animal kingdom. Although the biochemical components underlying these molecular clocks have been characterized in certain detail, the mechanisms used by clock neurons to convey information to downstream pathways controlling behavior remain elusive. In the fruit fly, a subset of circadian neurons called the small ventral lateral neurons (sLNvs) are capable of synchronizing other clock cells relying on a neuropeptide named pigment dispersing factor (PDF). In addition, a number of years ago we described another mechanism as a possible candidate for contributing to the transmission of information downstream of the sLNvs, involving adult-specific remodeling of the axonal terminals of these circadian neurons. In this manuscript we describe some of the molecular events that lead to this striking form of structural plasticity on a daily basis.
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DOI：
10.1126/science.1202839
发表时间：
2011-06-24
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Bushey D;Tononi G;Cirelli C
通讯作者：
Cirelli C
影响因子：
3.7
作者：
Barth, Martin;Schultze, Michael;Strauss, Roland
通讯作者：
Strauss, Roland
影响因子：
64.8
作者：
Grima, B;Chèlot, E;Rouyer, F
通讯作者：
Rouyer, F
DOI：
10.1098/rstb.2010.0409
发表时间：
2011-07-27
影响因子：
6.3
作者：
Hut, R. A.;Beersma, D. G. M.
通讯作者：
Beersma, D. G. M.
影响因子：
9.2
作者：
Axel Gorostiza, E.;Depetris-Chauvin, Ana;Frenkel, Lia;Pirez, Nicolas;Fernanda Ceriani, Maria
通讯作者：
Fernanda Ceriani, Maria