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首页> 外文期刊>The Journal of Neuroscience: The Official Journal of the Society for Neuroscience >Dystrobrevin controls neurotransmitter release and muscle Ca(2+) transients by localizing BK channels in Caenorhabditis elegans.
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Dystrobrevin controls neurotransmitter release and muscle Ca(2+) transients by localizing BK channels in Caenorhabditis elegans.

机译：Dystrobrevin通过定位秀丽隐杆线虫中的BK通道来控制神经递质释放和肌肉Ca（2+）瞬变。

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摘要

Dystrobrevin is a major component of a dystrophin-associated protein complex. It is widely expressed in mammalian tissues, including the nervous system, in which it is localized to the presynaptic nerve terminal with unknown function. In a genetic screen for suppressors of a lethargic phenotype caused by a gain-of-function isoform of SLO-1 in Caenorhabditis elegans, we isolated multiple loss-of-function (lf) mutants of the dystrobrevin gene dyb-1.dyb-1(lf) phenocopied slo-1(lf), causing increased neurotransmitter release at the neuromuscular junction, increased frequency of Ca(2+) transients in body-wall muscle, and abnormal locomotion behavior. Neuron- and muscle-specific rescue experiments suggest that DYB-1 is required for SLO-1 function in both neurons and muscle cells. DYB-1 colocalized with SLO-1 at presynaptic sites in neurons and dense body regions in muscle cells, and dyb-1(lf) caused SLO-1 mislocalization in both types of cells without altering SLO-1 protein level. The neuronal phenotypes of dyb-1(lf) were partially rescued by mouse alpha-dystrobrevin-1. These observations revealed novel functions of the BK channel in regulating muscle Ca(2+) transients and of dystrobrevin in controlling neurotransmitter release and muscle Ca(2+) transients by localizing the BK channel.
机译：肌营养不良蛋白是肌营养不良蛋白相关蛋白复合物的主要成分。它在包括神经系统在内的哺乳动物组织中广泛表达，其中它定位于功能未知的突触前神经末梢。在由秀丽隐杆线虫中SLO-1功能获得同工型引起的嗜睡表型抑制基因的遗传筛选中，我们分离了dystrobrevin基因dyb-1.dyb-1的多个功能丧失（lf）突变体。 （lf）表型slo-1（lf），导致神经肌肉接头处神经递质的释放增加，体壁肌肉中Ca（2+）瞬变的频率增加以及异常的运动行为。神经元和肌肉特定的救援实验表明，DYB-1是神经元和肌肉细胞中SLO-1功能所必需的。 DYB-1与SLO-1在神经元的突触前位点和肌肉细胞的密集体区共定位，而dyb-1（lf）导致SLO-1在这两种类型的细胞中均未定位，而不会改变SLO-1蛋白的水平。 dyb-1（lf）的神经元表型被小鼠α-dystrobrevin-1挽救了一部分。这些观察结果揭示了BK通道在调节肌肉Ca（2+）瞬变中的新功能，以及dystrobrevin在通过定位BK通道控制神经递质释放和肌肉Ca（2+）瞬变中的新功能。

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