A novel pathway for MuSK to induce key genes in neuromuscular synapse formation.
A novel pathway for MuSK to induce key genes in neuromuscular synapse formation.
复制标题
麝香诱导神经肌肉突触形成中的关键基因的新途径。
DOI：
10.1083/jcb.200210156
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发表时间：
2003-05-26
影响因子：
7.8
通讯作者：
Brenner, HR
中科院分区：
文献类型：
--
作者：
Lacazette, E;Le Calvez, S;Gajendran, N;Brenner, HR
在发育中的神经肌肉接头处，聚集蛋白受体MuSK是由来自神经的聚集蛋白诱导的突触下分化的中心组织者。麝香本身的表达也受神经调节，但所涉及的机制尚不清楚。在这里，我们分析了麝香启动子报告构建体在体内肌肉纤维和培养的肌管中的激活，使用多种组合的表达载体转染潜在的信号传导成分。我们表明，神经元聚集蛋白通过激活MuSK调节麝香的表达通过两种途径：聚集蛋白诱导的肌肉源性神经调节蛋白（NRG）-1/ErbB的组装，该途径被认为是调节突触处乙酰胆碱受体（AChR）表达，并通过直接分流涉及聚集蛋白诱导的Rac激活。这两种途径汇聚到麝香启动子中的相同调节元件上，该麝香启动子也被认为赋予AChR亚基基因突触特异性表达。通过这种方式，建立了一个正反馈信号循环，当脉冲传输发挥作用时，该循环维持突触处的麝香表达。同样的通路也用于调节AChR β的突触表达。我们认为，新的途径稳定突触早期发育，而NRG/ErbB途径支持维护成熟的突触。
At the developing neuromuscular junction the Agrin receptor MuSK is the central organizer of subsynaptic differentiation induced by Agrin from the nerve. The expression of musk itself is also regulated by the nerve, but the mechanisms involved are not known. Here, we analyzed the activation of a musk promoter reporter construct in muscle fibers in vivo and in cultured myotubes, using transfection of multiple combinations of expression vectors for potential signaling components. We show that neuronal Agrin by activating MuSK regulates the expression of musk via two pathways: the Agrin-induced assembly of muscle-derived neuregulin (NRG)-1/ErbB, the pathway thought to regulate acetylcholine receptor (AChR) expression at the synapse, and via a direct shunt involving Agrin-induced activation of Rac. Both pathways converge onto the same regulatory element in the musk promoter that is also thought to confer synapse-specific expression to AChR subunit genes. In this way, a positive feedback signaling loop is established that maintains musk expression at the synapse when impulse transmission becomes functional. The same pathways are used to regulate synaptic expression of AChRɛ . We propose that the novel pathway stabilizes the synapse early in development, whereas the NRG/ErbB pathway supports maintenance of the mature synapse.
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影响因子：
11.4
作者：
Altiok, N;Altiok, S;Changeux, JP
通讯作者：
Changeux, JP
影响因子：
2.7
作者：
Bowen, DC;Park, JS;DiStefano, PS
通讯作者：
DiStefano, PS
影响因子：
3.5
作者：
Hashemolhosseini, S;Moore, C;Brenner, HR
通讯作者：
Brenner, HR
影响因子：
56.9
作者：
Batchelor, AH;Piper, DE;Wolberger, C
通讯作者：
Wolberger, C
DOI：
10.1073/pnas.92.23.10624
发表时间：
1995-11-07
影响因子：
11.1
作者：
KOIKE, S;SCHAEFFER, L;CHANGEUX, JP
通讯作者：
CHANGEUX, JP