The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses.

The balance between capture and dissociation of presynaptic proteins controls the spatial distribution of synapses.
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突触前蛋白质的捕获和解离之间的平衡控制着突触的空间分布

DOI:
10.1016/j.neuron.2013.04.035
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发表时间:
2013-06-19
期刊:
影响因子:
16.2
通讯作者:
Shen K
Shen K
中科院分区:
医学1区
文献类型:
--
作者:
Wu YE;Huo L;Maeder CI;Feng W;Shen K

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突触的位置、大小和数量严重影响神经连接的特异性和强度。在轴突中,突触小泡(SV)和活性区(AZ)蛋白由分子马达运输并在离散的突触前位点积累。对于协调突触前蛋白质运输和沉积以实现突触物质正确分布的机制知之甚少。在这里,我们表明 SV 和 AZ 蛋白表现出广泛的协同转运并经历频繁的暂停。在轴突和突触暂停位点,移动传输包的捕获和解离之间的平衡决定了突触前组装的程度。小 G 蛋白 ARL-8 通过促进解离来抑制组装,而 JNK 激酶途径和 AZ 组装蛋白则抑制解离。此外,ARL-8 直接与 UNC-104/KIF1A 电机结合以限制捕获效率。轴突运输和局部组装之间二分法的分子调节共同控制着突触形成和维持的重要方面。
The location, size and number of synapses critically influence the specificity and strength of neural connections. In axons, synaptic vesicle (SV) and active zone (AZ) proteins are transported by molecular motors and accumulate at discrete presynaptic loci. Little is known about the mechanisms coordinating presynaptic protein transport and deposition to achieve proper distribution of synaptic material. Here we show that SV and AZ proteins exhibit extensive co-transport and undergo frequent pauses. At the axonal and synaptic pause sites, the balance between the capture and dissociation of mobile transport packets determines the extent of presynaptic assembly. The small G protein ARL-8 inhibits assembly by promoting dissociation, while a JNK kinase pathway and AZ assembly proteins inhibit dissociation. Furthermore, ARL-8 directly binds to the UNC-104/KIF1A motor to limit the capture efficiency. Together, molecular regulation of the dichotomy between axonal trafficking and local assembly controls vital aspects of synapse formation and maintenance.
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影响因子: --
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