The function of mitochondria in presynaptic development at the neuromuscular junction
The function of mitochondria in presynaptic development at the neuromuscular junction
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DOI：
10.1091/mbc.e07-05-0515
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发表时间：
2008-01-01
影响因子：
3.3
通讯作者：
Peng, H. Benjamin
中科院分区：
文献类型：
--
作者：
Lee, Chi Wai;Peng, H. Benjamin
在脊椎动物神经肌肉接头处的突触前神经末梢中富含具有高膜电位（Delta Psi（m））的线粒体，但这些局部突触线粒体的确切功能仍不清楚。在这里，我们研究了线粒体Delta Psi（m）和突触特化的发展之间的相关性。利用线粒体Delta Psi（m）敏感探针JC-1，我们发现爪蟾脊髓神经元的Delta Psi（m）可被肌酸可逆地升高，并被FCCP抑制。沿着沿着幼稚神经突，预先存在的突触囊泡（SV）簇与线粒体Delta Psi（m）呈正相关，表明线粒体活性在突触发生中的潜在调节作用。线粒体ATP合成酶抑制剂寡霉素，而不是线粒体Na+/Ca 2+交换抑制剂CGP-37157，抑制生长因子包被的珠子诱导的SV的聚类，表明线粒体活性在突触前发育中的特定作用。FCCP或寡霉素可抑制磁珠诱导的局部F-actin沿沿着脊神经突起的组装。我们的研究结果表明，突触前线粒体的一个关键作用是提供ATP的组装肌动蛋白细胞骨架参与组装的突触前专业化，包括群集的SV和线粒体本身。
Mitochondria with high membrane potential (Delta Psi(m)) are enriched in the presynaptic nerve terminal at vertebrate neuromuscular junctions, but the exact function of these localized synaptic mitochondria remains unclear. Here, we investigated the correlation between mitochondrial Delta Psi(m) and the development of synaptic specializations. Using mitochondrial Delta Psi(m)-sensitive probe JC-1, we found that Delta Psi(m) in Xenopus spinal neurons could be reversibly elevated by creatine and suppressed by FCCP. Along naive neurites, preexisting synaptic vesicle (SV) clusters were positively correlated with mitochondrial Delta Psi(m), suggesting a potential regulatory role of mitochondrial activity in synaptogenesis. Indicating a specific role of mitochondrial activity in presynaptic development, mitochondrial ATP synthase inhibitor oligomycin, but not mitochondrial Na+/Ca2+ exchanger inhibitor CGP-37157, inhibited the clustering of SVs induced by growth factor-coated beads. Local F-actin assembly induced along spinal neurites by beads was suppressed by FCCP or oligomycin. Our results suggest that a key role of presynaptic mitochondria is to provide ATP for the assembly of actin cytoskeleton involved in the assembly of the presynaptic specialization including the clustering of SVs and mitochondria themselves.