Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment.
Synaptotagmin 7 functions as a Ca2+-sensor for synaptic vesicle replenishment.
复制标题
Synaptotagmin 7充当CA2+传感器，用于突触囊泡补充。
DOI：
10.7554/elife.01524
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发表时间：
2014-02-25
期刊：
影响因子：
7.7
通讯作者：
Chapman ER
中科院分区：
文献类型：
--
作者：
Liu H;Bai H;Hui E;Yang L;Evans CS;Wang Z;Kwon SE;Chapman ER
突触素(Syt)7是在所有后生动物中发现的三种syt亚型之一；它广泛表达，但其在神经元中的功能尚不清楚。在这里，我们解析了钙依赖和非钙依赖的突触小泡(SV)的补充途径，发现Syt7在钙依赖的途径中起着选择性和关键的作用。破坏与Syt 7的钙结合的突变取消了这一功能，表明Syt 7作为钙补充传感器发挥作用。钙离子结合蛋白钙调蛋白(CaM)也与SV的补充有关，我们发现Syt7的丢失被CaM拮抗剂所抑制。此外，我们还发现，Syt7以一种高度特异和钙依赖的方式与CaM结合；这种相互作用需要Syt7内完整的钙结合部位。这些数据表明，两个保守的钙结合蛋白Syt7和CaM的复合体是突触前神经末梢SV补充的关键调节因子。DOI：http://dx.doi.org/10.7554/eLife.01524.001神经元在称为突触的交界处相互通信。一个被称为动作电位的电信号到达第一个神经元时，会触发被称为神经递质的化学物质释放到突触中。然后，这些化学物质扩散到神经元之间的缝隙中，并与第二个细胞上的受体结合。神经递质分子储存在第一个细胞的囊泡中，囊泡通过与细胞膜融合释放其内容物。在融合事件之后，神经元必须补充它们的囊泡储备，以确保它们为下一个动作电位的到来做好准备。这一补充过程包括钙依赖途径和非钙依赖途径。一种名为钙调蛋白的蛋白质与钙离子结合，在第一条途径中起着重要作用。现在，刘等人。研究表明，另一种蛋白质，突触素7，在突触小泡的补充中也起着关键作用，可能是作为钙离子的传感器。此外，Liu et al.发现突触素7和钙调蛋白相互结合形成一个复合体，这表明钙依赖的补充途径受该复合体的调控。突触素是一个由17种蛋白质组成的家族，其中3种存在于所有动物身上。已知其中两个在突触中发挥作用，但第三个--突触素7--的作用尚不清楚。除了对突触小泡的补充提供了更完整的理解外，Liu等人的工作还提供了一个更完整的了解。还提供了关于所有动物中存在的突触素的作用的拼图的最后一块。DOI：http://dx.doi.org/10.7554/eLife.01524.002
Synaptotagmin (syt) 7 is one of three syt isoforms found in all metazoans; it is ubiquitously expressed, yet its function in neurons remains obscure. Here, we resolved Ca2+-dependent and Ca2+-independent synaptic vesicle (SV) replenishment pathways, and found that syt 7 plays a selective and critical role in the Ca2+-dependent pathway. Mutations that disrupt Ca2+-binding to syt 7 abolish this function, suggesting that syt 7 functions as a Ca2+-sensor for replenishment. The Ca2+-binding protein calmodulin (CaM) has also been implicated in SV replenishment, and we found that loss of syt 7 was phenocopied by a CaM antagonist. Moreover, we discovered that syt 7 binds to CaM in a highly specific and Ca2+-dependent manner; this interaction requires intact Ca2+-binding sites within syt 7. Together, these data indicate that a complex of two conserved Ca2+-binding proteins, syt 7 and CaM, serve as a key regulator of SV replenishment in presynaptic nerve terminals. DOI: http://dx.doi.org/10.7554/eLife.01524.001 Neurons communicate with one another at junctions called synapses. The arrival of an electrical signal called an action potential at the first neuron triggers the release of chemicals called neurotransmitters into the synapse. These chemicals then diffuse across the gap between the neurons and bind to receptors on the second cell. The neurotransmitter molecules are stored in the first cell in packages known as vesicles, which release their contents by fusing with the cell membrane. Following a fusion event, neurons must replenish their vesicle stocks to ensure that they are ready for the arrival of the next action potential. This replenishment process is known to involve a calcium-dependent pathway and a calcium-independent pathway. A protein called calmodulin, that binds calcium ions, has an important role in the first of these pathways. Now, Liu et al. have shown that another protein, synaptotagmin 7, also has a key role in the replenishment of synaptic vesicles, possibly as a sensor for calcium ions. Moreover, Liu et al. found that synaptotagmin 7 and calmodulin bind to each other to form a complex, which suggests that the calcium-dependent replenishment pathway is regulated by this complex. The synaptotagmins are a family of 17 proteins, three of which are present in all animals. Two of these were known to have roles in synapses, but the role of the third—synaptotagmin 7—had been unclear. In addition to providing a more complete understanding of the replenishment of synaptic vesicles, the work of Liu et al. also supplies the final piece of the jigsaw regarding the role of the synaptotagmins that are present in all animals. DOI: http://dx.doi.org/10.7554/eLife.01524.002