Apparent calcium dependence of vesicle recruitment
Apparent calcium dependence of vesicle recruitment
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囊泡募集的明显钙依赖性
DOI：
10.1113/jp275911
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发表时间：
2018
期刊：
影响因子：
--
通讯作者：
Hallermann S
中科院分区：
文献类型：
--
作者：
Ritzau-Jost A;Jablonski L;Viotti J;Lipstein N;Eilers J;Hallermann S
突触传递依赖于神经递质填充囊泡向突触前释放位点的募集。细胞内钙缓冲的增加减缓了突触抑制后的恢复，这表明囊泡募集是一个钙依赖的过程。然而，囊泡募集的分子机制只在一些突触中被研究过。我们研究了钙在小脑苔藓纤维到颗粒细胞突触的囊泡募集中的作用。我们发现细胞内钙缓冲的增加减缓了生理刺激后抑郁症的恢复。然而，这种恢复在很大程度上抵抗了先前显示的介导钙依赖性囊泡募集的分子途径的扰动。此外，我们发现两个囊泡池具有不同的招募速度，并表明包含两个具有不同钙独立招募率的囊泡池的模型可以解释我们的数据。在这个框架中，增加的钙缓冲阻止了本质上快速募集的囊泡的释放，但并不改变囊泡本身的募集率。在持续的突触传递过程中，新的充满递质的囊泡被募集到释放位点，抵消了囊泡的消耗，从而抵消了突触的抑制。升高的细胞内Ca2+浓度被认为可以加速许多突触的囊泡招募速率。这一结论通常是基于增加细胞内Ca2+缓冲减缓从突触抑制恢复的发现。然而，仅在一些突触中分析了活性依赖性囊泡募集加速的分子机制。利用突触后记录的生理刺激模式和突触前记录的阶跃去极化，我们研究了小脑苔藓纤维钮扣的囊泡募集。我们发现增加的细胞内Ca2+缓冲显著减缓了抑郁症的恢复。然而，对钙调素或钙调素- munc13途径的药理学和遗传干扰，已经被提出介导Ca2+依赖性的囊泡募集，几乎不影响抑郁后的囊泡恢复。此外，我们发现小脑苔藓纤维钮扣有两个囊泡池：快速融合的囊泡恢复缓慢，缓慢融合的囊泡恢复迅速。最后，采用这两种具有Ca2+独立招募率的囊泡池的模型可以解释Ca2+缓冲增加后抑郁症恢复缓慢的原因。我们的数据不排除calmodulin-Munc13通路参与强刺激或其他分子通路介导小脑苔藓纤维钮扣Ca2+依赖性囊泡募集。然而，我们证明了建立良好的双池模型预测了明显的Ca2+依赖性囊泡招募。因此，之前的结论Ca2+依赖囊泡募集仅仅基于增加的细胞内Ca2+缓冲应该谨慎考虑。
Key pointsSynaptic transmission relies on the recruitment of neurotransmitter‐filled vesicles to presynaptic release sites. Increased intracellular calcium buffering slows the recovery from synaptic depression, suggesting that vesicle recruitment is a calcium‐dependent process.However, the molecular mechanisms of vesicle recruitment have only been investigated at some synapses.We investigate the role of calcium in vesicle recruitment at the cerebellar mossy fibre to granule cell synapse. We find that increased intracellular calcium buffering slows the recovery from depression following physiological stimulation. However, the recovery is largely resistant to perturbation of the molecular pathways previously shown to mediate calcium‐dependent vesicle recruitment.Furthermore, we find two pools of vesicles with different recruitment speeds and show that models incorporating two pools of vesicles with different calcium‐independent recruitment rates can explain our data. In this framework, increased calcium buffering prevents the release of intrinsically fast‐recruited vesicles but does not change the vesicle recruitment rates themselves.AbstractDuring sustained synaptic transmission, recruitment of new transmitter‐filled vesicles to the release site counteracts vesicle depletion and thus synaptic depression. An elevated intracellular Ca2+concentration has been proposed to accelerate the rate of vesicle recruitment at many synapses. This conclusion is often based on the finding that increased intracellular Ca2+buffering slows the recovery from synaptic depression. However, the molecular mechanisms of the activity‐dependent acceleration of vesicle recruitment have only been analysed at some synapses. Using physiological stimulation patterns in postsynaptic recordings and step depolarizations in presynaptic bouton recordings, we investigate vesicle recruitment at cerebellar mossy fibre boutons. We show that increased intracellular Ca2+buffering slows recovery from depression dramatically. However, pharmacological and genetic interference with calmodulin or the calmodulin–Munc13 pathway, which has been proposed to mediate Ca2+‐dependence of vesicle recruitment, barely affects vesicle recovery from depression. Furthermore, we show that cerebellar mossy fibre boutons have two pools of vesicles: rapidly fusing vesicles that recover slowly and slowly fusing vesicles that recover rapidly. Finally, models adopting such two pools of vesicles with Ca2+‐independent recruitment rates can explain the slowed recovery from depression upon increased Ca2+buffering. Our data do not rule out the involvement of the calmodulin–Munc13 pathway during stronger stimuli or other molecular pathways mediating Ca2+‐dependent vesicle recruitment at cerebellar mossy fibre boutons. However, we show that well‐established two‐pool models predict an apparent Ca2+‐dependence of vesicle recruitment. Thus, previous conclusions of Ca2+‐dependent vesicle recruitment based solely on increased intracellular Ca2+buffering should be considered with caution.
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从持有突触的花萼中进行了一些微妙的教训。
影响因子：
3.4
作者：
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通讯作者：
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影响因子：
5.5
作者：
FORSYTHE, ID
通讯作者：
FORSYTHE, ID
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影响因子：
2.5
作者：
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通讯作者：
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DOI：
10.1523/jneurosci.21-02-00462.2001
发表时间：
2001-01
期刊：
The Journal of Neuroscience
影响因子：
--
作者：
T. Sakaba;E. Neher
通讯作者：
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影响因子：
5.3
作者：
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通讯作者：
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