神经海滩蛋白对神经肌肉突触传递至关重要。
Neurobeachin is essential for neuromuscular synaptic transmission.
作者信息
Su Yuhua, Balice-Gordon Rita J, Hess Darren M, Landsman Douglas S, Minarcik Jeremy, Golden Jeffrey, Hurwitz Ivy, Liebhaber Stephen A, Cooke Nancy E
机构信息
Department of Genetics and Medicine, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA.
出版信息
J Neurosci. 2004 Apr 7;24(14):3627-36. doi: 10.1523/JNEUROSCI.4644-03.2004.
Abstract
We report a random disruption in the mouse genome that resulted in lethal paralysis in homozygous newborns. The disruption blocked expression of neurobeachin, a protein containing a BEACH (beige and Chediak-Higashi) domain implicated in synaptic vesicle trafficking and an AKAP (A-kinase anchor protein) domain linked to localization of cAMP-dependent protein kinase activity. nbea-null mice demonstrated a complete block of evoked synaptic transmission at neuromuscular junctions, whereas nerve conduction, synaptic structure, and spontaneous synaptic vesicle release were completely normal. These findings support an essential role for neurobeachin in evoked neurotransmitter release at neuromuscular junctions and suggest that it plays an important role in synaptic transmission.
摘要
我们报道了小鼠基因组中的一个随机破坏事件，该事件导致纯合新生小鼠出现致命性麻痹。这种破坏阻断了神经beachin的表达，神经beachin是一种蛋白质，包含一个与突触小泡运输有关的BEACH（米色和切迪阿克-东希）结构域以及一个与环磷酸腺苷依赖性蛋白激酶活性定位相关的AKAP（A激酶锚定蛋白）结构域。nbea基因敲除小鼠在神经肌肉接头处表现出诱发突触传递的完全阻断，而神经传导、突触结构和自发突触小泡释放则完全正常。这些发现支持了神经beachin在神经肌肉接头处诱发神经递质释放中起关键作用，并表明它在突触传递中发挥重要作用。
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本文引用的文献
1
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J Med Genet. 2003 May;40(5):352-6. doi: 10.1136/jmg.40.5.352.
2
Activity-dependent synaptic plasticity: insights from neuromuscular junctions.活动依赖型突触可塑性：来自神经肌肉接头的见解
Neuroscientist. 2002 Oct;8(5):414-22. doi: 10.1177/107385802236970.
3
Crystal structure of the BEACH domain reveals an unusual fold and extensive association with a novel PH domain.BEACH结构域的晶体结构揭示了一种不同寻常的折叠方式以及与一种新型PH结构域的广泛关联。
EMBO J. 2002 Sep 16;21(18):4785-95. doi: 10.1093/emboj/cdf502.
4
Snares and Munc18 in synaptic vesicle fusion.突触小泡融合中的圈套蛋白和Munc18蛋白
Nat Rev Neurosci. 2002 Aug;3(8):641-53. doi: 10.1038/nrn898.
5
Meaningless minis? Mechanisms of neurotransmitter-receptor clustering.
Trends Neurosci. 2002 Aug;25(8):383-5. doi: 10.1016/s0166-2236(02)02197-5.
6
rugose (rg), a Drosophila A kinase anchor protein, is required for retinal pattern formation and interacts genetically with multiple signaling pathways.粗糙（rg）是一种果蝇A激酶锚定蛋白，是视网膜模式形成所必需的，并且在遗传上与多种信号通路相互作用。
Genetics. 2002 Jun;161(2):693-710. doi: 10.1093/genetics/161.2.693.
7
Inhibition of spontaneous acetylcholine secretion by 2-chloroadenosine as revealed by a protein kinase inhibitor at the mouse neuromuscular junction.蛋白激酶抑制剂揭示2-氯腺苷对小鼠神经肌肉接头处乙酰胆碱自发分泌的抑制作用。
Br J Pharmacol. 2002 Apr;135(8):1897-902. doi: 10.1038/sj.bjp.0704653.
8
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Nat Neurosci. 2002 Jan;5(1):19-26. doi: 10.1038/nn783.
9
PKA, PKC, and AKAP localization in and around the neuromuscular junction.蛋白激酶A、蛋白激酶C和A激酶锚定蛋白在神经肌肉接头及其周围的定位。
BMC Neurosci. 2001;2:17. doi: 10.1186/1471-2202-2-17. Epub 2001 Oct 23.
10
SNARE function analyzed in synaptobrevin/VAMP knockout mice.在突触小泡蛋白/囊泡相关膜蛋白基因敲除小鼠中分析SNARE功能。
Science. 2001 Nov 2;294(5544):1117-22. doi: 10.1126/science.1064335.
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