Drosophila CAKI/CMG protein, a homolog of human CASK, is essential for regulation of neurotransmitter vesicle release.

Drosophila CAKI/CMG protein, a homolog of human CASK, is essential for regulation of neurotransmitter vesicle release.
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DOI:
10.1152/jn.00954.2004
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发表时间:
2005-08
影响因子:
2.5
通讯作者:
M. Zordan;M. Massironi;M. Ducato;G. te Kronnie;R. Costa;C. Reggiani;C. Chagneau;Jean-René Martin;A. Megighian
M. Zordan;M. Massironi;M. Ducato;G. te Kronnie;R. Costa;C. Reggiani;C. Chagneau;Jean-René Martin;A. Megighian
中科院分区:
医学3区
文献类型:
--
作者:
M. Zordan;M. Massironi;M. Ducato;G. te Kronnie;R. Costa;C. Reggiani;C. Chagneau;Jean-René Martin;A. Megighian

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脊椎动物CASK是膜相关鸟苷酸激酶(MAGUK)蛋白家族的成员。CASK存在于神经系统中,在神经系统中它与neurexin结合,neurexin是一种位于突触前膜中的跨膜蛋白。CASK的果蝇同源物是CAKI或CAMGUK。CAKI在幼虫和成虫的神经系统中表达。在成年果蝇中,caki的表达在视觉脑区域特别明显。为了阐明CASK的功能作用,我们在模式生物果蝇中使用了caki无效突变体。通过电生理方法,我们分析了,在成年苍蝇的神经肌肉接头(NMJ)的自发和诱发的神经递质释放,以及巨纤维通路和视觉系统的功能状态。我们发现,在caki突变体中,当突触活动被修改时,间接飞行肌NMJ的自发神经递质释放增加,巨纤维通路对连续刺激的反应受损,对单一和连续重复刺激的视网膜电图反应改变,视动行为异常。这些结果支持CAKI参与神经递质释放和神经系统功能。
Vertebrate CASK is a member of the membrane-associated guanylate kinase (MAGUK) family of proteins. CASK is present in the nervous system where it binds to neurexin, a transmembrane protein localized in the presynaptic membrane. The Drosophila homologue of CASK is CAKI or CAMGUK. CAKI is expressed in the nervous system of larvae and adult flies. In adult flies, the expression of caki is particularly evident in the visual brain regions. To elucidate the functional role of CASK, we employed a caki null mutant in the model organism Drosophila melanogaster. By means of electrophysiological methods, we analyzed, in adult flies, the spontaneous and evoked neurotransmitter release at the neuromuscular junction (NMJ) as well as the functional status of the giant fiber pathway and of the visual system. We found that in caki mutants, when synaptic activity is modified, the spontaneous neurotransmitter release of the indirect flight muscle NMJ was increased, the response of the giant fiber pathway to continuous stimulation was impaired, and electroretinographic responses to single and continuous repetitive stimuli were altered and optomotor behavior was abnormal. These results support the involvement of CAKI in neurotransmitter release and nervous system function.