The role of carcinine in signaling at the Drosophila photoreceptor synapse.
The role of carcinine in signaling at the Drosophila photoreceptor synapse.
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DOI：
10.1371/journal.pgen.0030206
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发表时间：
2007-12
期刊：
影响因子：
4.5
通讯作者：
Dolph PJ
中科院分区：
文献类型：
--
作者：
Gavin BA;Arruda SE;Dolph PJ
果蝇感光细胞长期以来一直作为研究人员的模型系统，专注于动物感觉神经元如何从周围环境接收信息并将这些信息转化为化学和电信息。对果蝇突变体的视网膜电图（ERG）分析有助于阐明参与感光细胞下游视觉转导途径的一些基因，现在很清楚感光细胞信号传导依赖于神经递质组胺的正确释放和再循环。虽然负责从突触间隙清除组胺及其代谢物癌的神经递质转运蛋白仍然未知，但任一底物转运蛋白的有力候选者是未表征的醉酒蛋白。醉酒基因 (ine) 编码一种假定的神经递质转运蛋白，该转运蛋白定位于果蝇的感光细胞，ine 的突变导致果蝇的 ERG 表型异常。乌木（果蝇中合成癌碱所需的基因）的功能丧失突变抑制了突变体ine ERG表型的成分，而果蝇中水解癌碱所需的基因tan（果蝇中癌碱水解所需的基因）的功能丧失突变对ine突变体中的ERG表型没有影响。我们还表明，通过给野生型果蝇喂食癌毒，我们可以复制突变ine ERGs的成分。最后，我们证明用 H3 受体激动剂或反向激动剂治疗可以挽救突变 ine ERG 表型的几个组成部分。在这里，我们提供了药理学和遗传上位证据，证明ine编码癌神经递质转运蛋白。我们还推测，在突变 ine ERG 迹线中观察到的振荡是假定的 H3 受体异常活性的结果。在神经系统信号传递过程中，各个神经细胞通过一种称为突触传递的复杂过程相互传递信息。这种通讯涉及将特定的神经递质释放到突触间隙，然后通过结合并激活特定的细胞表面受体来触发下游神经元的信号传导。为了终止神经元信号，必须快速从突触间隙去除神经递质。这是通过两种机制完成的：神经递质可以被降解或修饰，或者递质可以被突触前神经元吸收并包装到囊泡中以供重复使用。在果蝇 D. melanogaster 的复眼中，感光细胞对光做出反应，并将组胺释放到突触间隙。该信号通过从突触中去除组胺并将组胺酶促转化为癌碱而终止。我们已经证明，仅仅改变组胺神经递质是不够的，从光感受器突触中去除癌素也很重要。未能充分去除癌会导致视觉传导过程中的缺陷。此外，这项工作表明癌素本身通过调节组胺释放到突触来调节视力。
The Drosophila melanogaster photoreceptor cell has long served as a model system for researchers focusing on how animal sensory neurons receive information from their surroundings and translate this information into chemical and electrical messages. Electroretinograph (ERG) analysis of Drosophila mutants has helped to elucidate some of the genes involved in the visual transduction pathway downstream of the photoreceptor cell, and it is now clear that photoreceptor cell signaling is dependent upon the proper release and recycling of the neurotransmitter histamine. While the neurotransmitter transporters responsible for clearing histamine, and its metabolite carcinine, from the synaptic cleft have remained unknown, a strong candidate for a transporter of either substrate is the uncharacterized inebriated protein. The inebriated gene (ine) encodes a putative neurotransmitter transporter that has been localized to photoreceptor cells in Drosophila and mutations in ine result in an abnormal ERG phenotype in Drosophila. Loss-of-function mutations in ebony, a gene required for the synthesis of carcinine in Drosophila, suppress components of the mutant ine ERG phenotype, while loss-of-function mutations in tan, a gene necessary for the hydrolysis of carcinine in Drosophila, have no effect on the ERG phenotype in ine mutants. We also show that by feeding wild-type flies carcinine, we can duplicate components of mutant ine ERGs. Finally, we demonstrate that treatment with H3 receptor agonists or inverse agonists rescue several components of the mutant ine ERG phenotype. Here, we provide pharmacological and genetic epistatic evidence that ine encodes a carcinine neurotransmitter transporter. We also speculate that the oscillations observed in mutant ine ERG traces are the result of the aberrant activity of a putative H3 receptor. During signaling in the nervous system, individual nerve cells transfer information to one another by a complex process called synaptic transmission. This communication involves the release of a specific neurotransmitter into the synaptic cleft, which then triggers signaling in the downstream neuron by binding to and activating specific cell surface receptors. In order to terminate the neuronal signal, the neurotransmitter must be rapidly removed from the synaptic cleft. This is done by two mechanisms: the neurotransmitter can be degraded or modified, or the transmitter can be taken up by the presynaptic neuron and packaged into vesicles for reuse. In the compound eye of the fruitfly D. melanogaster, the photoreceptor cell responds to light and releases histamine into the synaptic cleft. This signal is terminated by the removal of histamine from the synapse and the enzymatic conversion of histamine to carcinine. We have shown that it is not sufficient just to modify the histamine neurotransmitter, but it is also important to remove carcinine from the photoreceptor synapse. The failure to adequately remove carcinine results in defects in the visual transduction process. Moreover, the work suggests that carcinine itself modulates vision by regulating histamine release into the synapse.
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DOI：
10.1124/jpet.104.072504
发表时间：
2005-01-01
影响因子：
3.5
作者：
Seyedi, N;Mackins, CJ;Levi, R
通讯作者：
Levi, R
DOI：
10.1073/pnas.75.1.515
发表时间：
1978-01-01
影响因子：
11.1
作者：
JAN, YN;JAN, LY
通讯作者：
JAN, LY
影响因子：
3.3
作者：
ARRANG, JM;GARBARG, M;SCHWARTZ, JC
通讯作者：
SCHWARTZ, JC
影响因子：
11.4
作者：
BURG, MG;SARTHY, PV;PAK, WL
通讯作者：
PAK, WL
影响因子：
3.6
作者：
Gomez-Ramirez, J;Ortiz, J;Blanco, I
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Blanco, I