Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise.
Active zone protein Bassoon co-localizes with presynaptic calcium channel, modifies channel function, and recovers from aging related loss by exercise.
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DOI：
10.1371/journal.pone.0038029
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Stanford JA
中科院分区：
文献类型：
--
作者：
Nishimune H;Numata T;Chen J;Aoki Y;Wang Y;Starr MP;Mori Y;Stanford JA
P/Q型电压依赖性钙通道（VDCCs）是成年哺乳动物神经肌肉接头（NMJ）突触传递所必需的;然而，VDCCs相对于啮齿动物NMJ活动区的突触下位置，以及VDCCs与活动区蛋白Bassoon相互作用的功能修饰仍然未知。在这里，我们表明P/Q型VDCC在NMJ突触前末梢内以点状模式分布，并与巴松管在三维上对齐。P/Q型VDCC和巴松管在NMJ中的这种分布模式与我们先前的研究一致，表明VDCC和巴松管的结合。此外，我们现在表明，P/Q型VDCCs和巴松管之间的相互作用显着抑制P/Q型VDCCs的失活特性，这表明可能是由巴松管增强的Ca 2+内流在NMJ有效的突触传递。然而，突触前巴松管水平显着衰减老年大鼠NMJ，这表明由于缺乏VDCC和巴松管之间的这种相互作用的VDCC功能的衰减。重要的是，通过两个月的肌肉等长力量训练，老年NMJ中降低的巴松管水平得到改善。训练增加了NMJ中的巴松管免疫反应性，而不影响突触大小。这些结果表明，P/Q型VDCCs优先聚集在NMJ活动区，并与活动区蛋白Bassoon一起在突触传递中发挥重要作用。这种分子机制随着年龄的增长而受损，这表明老年NMJ的突触功能发生了改变。但老年NMJ的大管音水平可以通过肌肉锻炼得到改善。
The P/Q-type voltage-dependent calcium channels (VDCCs) are essential for synaptic transmission at adult mammalian neuromuscular junctions (NMJs); however, the subsynaptic location of VDCCs relative to active zones in rodent NMJs, and the functional modification of VDCCs by the interaction with active zone protein Bassoon remain unknown. Here, we show that P/Q-type VDCCs distribute in a punctate pattern within the NMJ presynaptic terminals and align in three dimensions with Bassoon. This distribution pattern of P/Q-type VDCCs and Bassoon in NMJs is consistent with our previous study demonstrating the binding of VDCCs and Bassoon. In addition, we now show that the interaction between P/Q-type VDCCs and Bassoon significantly suppressed the inactivation property of P/Q-type VDCCs, suggesting that the Ca2+ influx may be augmented by Bassoon for efficient synaptic transmission at NMJs. However, presynaptic Bassoon level was significantly attenuated in aged rat NMJs, which suggests an attenuation of VDCC function due to a lack of this interaction between VDCC and Bassoon. Importantly, the decreased Bassoon level in aged NMJs was ameliorated by isometric strength training of muscles for two months. The training increased Bassoon immunoreactivity in NMJs without affecting synapse size. These results demonstrated that the P/Q-type VDCCs preferentially accumulate at NMJ active zones and play essential role in synaptic transmission in conjunction with the active zone protein Bassoon. This molecular mechanism becomes impaired by aging, which suggests altered synaptic function in aged NMJs. However, Bassoon level in aged NMJs can be improved by muscle exercise.
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影响因子：
16.2
作者：
Frank, Thomas;Rutherford, Mark A.;Strenzke, Nicola;Neef, Andreas;Pangrsic, Tina;Khimich, Darina;Fetjova, Anna;Gundelfinger, Eckart D.;Liberman, M. Charles;Harke, Benjamin;Bryan, Keith E.;Lee, Amy;Egner, Alexander;Riedel, Dietmar;Moser, Tobias
通讯作者：
Moser, Tobias
影响因子：
1.7
作者：
Billings SE;Clarke GL;Nishimune H
通讯作者：
Nishimune H
DOI：
10.1083/jcb.81.2.275
发表时间：
1979-05
期刊：
The Journal of cell biology
影响因子：
--
作者：
Heuser JE;Reese TS;Dennis MJ;Jan Y;Jan L;Evans L
通讯作者：
Evans L
影响因子：
3.3
作者：
Fahim, MA
通讯作者：
Fahim, MA
影响因子：
25
作者：
Kiyonaka, Shigeki;Wakamori, Minoru;Mori, Yasuo
通讯作者：
Mori, Yasuo