Pre and postsynaptic roles for Drosophila CASK

Pre and postsynaptic roles for Drosophila CASK
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DOI:
10.1016/j.mcn.2011.07.009
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发表时间:
2011-10-01
影响因子:
3.5
通讯作者:
Featherstone, David E.
Featherstone, David E.
中科院分区:
医学3区
文献类型:
--
作者:
Chen, Kaiyun;Featherstone, David E.

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CASK(钙/钙调蛋白依赖的丝氨酸蛋白激酶),在果蝇中也被称为Caki或Camguk/CMG,在线虫中被称为LIN-2,被认为在细胞-细胞连接的形成,特别是在突触中发挥着重要作用。为了了解CASK在突触形成和功能中的作用,我们在泛细胞和组织特异性操作CASK表达后,对果蝇胚胎和幼虫谷氨酸能神经肌肉接头(NMJ)进行了功能和形态分析。我们的结果表明,果蝇木桶与突触前膜和突触后膜都有联系。失去突触前桶导致诱发的突触传递减少,自发突触事件减少,突触囊泡循环减少。这些变化伴随着突触数量的减少,但总体NMJ大小没有变化。另一方面,失去突触后桶会导致自发突触电流幅度降低,谷氨酸门控电流变小。这些变化伴随着突触后谷氨酸受体的丢失,但受体丢失是亚型特有的:在木桶突变体中只丢失含有GluRIIA亚单位的受体。含有GluRIIB的受体未受影响。(C)2011 Elsevier Inc.保留所有权利。
CASK ('calcium/calmodulin-dependent serine protein kinase'), also known in Drosophila as 'Caki' or 'Camguk/CMG', and in C elegans as 'Lin-2', is thought to play an important role in cell-cell junction formation and at synapses in particular. To understand the role of CASK in synapse formation and function, we functionally and morphologically analyzed Drosophila embryonic and larval glutamatergic neuromuscular junctions (NMJs) after pan-cellular and tissue-specific manipulation of CASK expression. Our results show that Drosophila CASK is associated with both pre and postsynaptic membranes. Loss of presynaptic CASK led to less evoked synaptic transmission, fewer spontaneous synaptic events, and reduced synaptic vesicle cycling. These changes were accompanied by a reduction in the number of synapses but no change in overall NMJ size. Loss of postsynaptic CASK, on the other hand, caused reduced spontaneous synaptic current amplitudes and smaller glutamate-gated currents. These changes were accompanied by loss of postsynaptic glutamate receptors, but the receptor loss was subtype-specific: Only receptors containing GluRIIA subunits were lost in CASK mutants. Receptors containing GluRIIB were unaffected. (C) 2011 Elsevier Inc. All rights reserved.