Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.
Activity of nAChRs containing alpha9 subunits modulates synapse stabilization via bidirectional signaling programs.
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DOI：
10.1002/dneu.20753
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发表时间：
2009-12
影响因子：
3
通讯作者：
Vetter, Douglas E.
中科院分区：
文献类型：
--
作者：
Murthy, Vidya;Taranda, Julian;Belen Elgoyhen, A.;Vetter, Douglas E.
虽然神经肌肉连接处胆碱能突触的突触形成程序是众所周知的，但参与非神经肌肉尼古丁突触发育的蛋白质的身份或动态表达模式知之甚少。我们之前已经证实在成年耳蜗中尼古丁乙酰胆碱受体(nAChR) α9亚基表达缺失后突触前末端形态异常。然而，这些变化背后的分子机制仍然不清楚。为了更好地了解突触的形成和胆碱能活性在内耳突触发生中的作用，我们利用nAChR α9亚基null小鼠。在这只小鼠中，功能性乙酰胆碱（ACh）神经传递到毛细胞是完全沉默的。结果表明，α9缺失小鼠外毛细胞突触极有一个过早的、渗出的神经支配，与渗出接触期间细胞粘附蛋白的延迟表达相一致。异位神经支配的崩溃与小鼠年龄相关的高表达模式一致。此外，我们记录了α9缺失小鼠突触前囊泡循环/运输机制的表达变化，这表明神经支配目标（毛细胞）和被毛细胞nAChR活性修饰的突触前末端之间存在双向信息流。nAChR活性的丧失可能会改变转录活性，因为在成年α9缺失小鼠中，CREB结合蛋白表达的降低与N-Cadherin表达的增加一致。最后，通过表达非脱敏α9 l9t点突变体nAChR亚基的小鼠，我们发现nAChR活性的增加驱动突触神经亢进。
Although the synaptogenic program for cholinergic synapses of the neuromuscular junction is well known, little is known of the identity or dynamic expression patterns of proteins involved in non-neuromuscular nicotinic synapse development. We have previously demonstrated abnormal presynaptic terminal morphology following loss of nicotinic acetylcholine receptor (nAChR) α9 subunit expression in adult cochleae. However, the molecular mechanisms underlying these changes have remained obscure. To better understand synapse formation and the role of cholinergic activity in the synaptogenesis of the inner ear, we exploit the nAChR α9 subunit null mouse. In this mouse, functional acetylcholine (ACh) neurotransmission to the hair cells is completely silenced. Results demonstrate a premature, effusive innervation to the synaptic pole of the outer hair cells in α9 null mice coinciding with delayed expression of cell adhesion proteins during the period of effusive contact. Collapse of the ectopic innervation coincides with an age-related hyperexpression pattern in the null mice. In addition, we document changes in expression of presynaptic vesicle recycling/trafficking machinery in the α9 null mice that suggests a bidirectional information flow between the target of the neural innervation (the hair cells) and the presynaptic terminal that is modified by hair cell nAChR activity. Loss of nAChR activity may alter transcriptional activity, as CREB binding protein expression is decreased coincident with the increased expression of N-Cadherin in the adult α9 null mice. Finally, by using mice expressing the nondesensitizing α9 L9′T point mutant nAChR subunit, we show that increased nAChR activity drives synaptic hyperinnervation.
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DOI：
10.1007/s10162-005-0018-3
发表时间：
2005-12-01
影响因子：
2.4
作者：
Bergeron, AL;Schrader, A;Simmons, DD
通讯作者：
Simmons, DD
影响因子：
16.2
作者：
Chang, KT;Berg, DK
通讯作者：
Berg, DK
DOI：
10.1083/jcb.200212140
发表时间：
2003-05-26
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bloom O;Evergren E;Tomilin N;Kjaerulff O;Löw P;Brodin L;Pieribone VA;Greengard P;Shupliakov O
通讯作者：
Shupliakov O
突触时的钙粘蛋白和Catenin：突触发生和突触可塑性中的作用。
影响因子：
15.9
作者：
Arikkath, Jyothi;Reichardt, Louis F.
通讯作者：
Reichardt, Louis F.
影响因子：
16.2
作者：
HATA, Y;DAVLETOV, B;SUDHOF, TC
通讯作者：
SUDHOF, TC