RIC-7 promotes neuropeptide secretion.

RIC-7 promotes neuropeptide secretion.
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DOI:
10.1371/journal.pgen.1002464
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发表时间:
2012-01
期刊:
影响因子:
4.5
通讯作者:
Kaplan JM
Kaplan JM
中科院分区:
生物学2区
文献类型:
--
作者:
Hao Y;Hu Z;Sieburth D;Kaplan JM

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神经递质和神经肽的分泌分别由不同的分泌细胞器、突触囊泡(SVs)和致密核囊泡(DCVs)的胞吐介导。相对而言,对SV和DCV分泌的差异调节因素知之甚少。在这里,我们鉴定了一种新的蛋白质RIC-7,它是秀丽隐杆线虫神经肽分泌所必需的。RIC-7蛋白在所有神经元中表达,并定位于突触前终末。成像、电生理和行为分析表明,ric-7突变体的乙酰胆碱释放正常,而神经肽释放明显减少。这些结果表明,RIC-7促进了dcv介导的分泌。神经肽产生与行为状态(如情绪或食欲)变化相关的回路活动的长期变化;因此,人们对识别神经肽分泌所需的分子非常感兴趣。在这里,我们发现一种新的神经元蛋白RIC-7促进秀丽隐杆线虫神经肽的分泌,但对神经递质分泌只有微弱的影响。ric7在其他几种线虫中是保守的;然而,在其他测序基因组中未发现同源蛋白。这些结果表明,负责神经肽分泌的机制比神经递质和神经肽分泌所需的因素进化得更晚。
Secretion of neurotransmitters and neuropeptides is mediated by exocytosis of distinct secretory organelles, synaptic vesicles (SVs) and dense core vesicles (DCVs) respectively. Relatively little is known about factors that differentially regulate SV and DCV secretion. Here we identify a novel protein RIC-7 that is required for neuropeptide secretion in Caenorhabditis elegans. The RIC-7 protein is expressed in all neurons and is localized to presynaptic terminals. Imaging, electrophysiology, and behavioral analysis of ric-7 mutants indicates that acetylcholine release occurs normally, while neuropeptide release is significantly decreased. These results suggest that RIC-7 promotes DCV–mediated secretion. Neuropeptides produce prolonged changes in circuit activity that are associated with changes in behavioral states (e.g. mood or appetite); consequently, there is great interest in identifying molecules that are required for neuropeptide secretion. Here we show that a novel neuronal protein RIC-7 promotes neuropeptide secretion in C. elegans but has only subtle effects on neurotransmitter secretion. RIC-7 is conserved in several other nematodes; however, homologous proteins are not found in other sequenced genomes. These results suggest that the machinery responsible for neuropeptide secretion evolved more recently than factors that are required for both neurotransmitter and neuropeptide secretion.
分析突触蛋白鉴定了胰岛素分泌和寿命的调节剂。
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