Palfrey H C, Artalejo C R
Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
Neuroscience. 1998 Apr;83(4):969-89. doi: 10.1016/s0306-4522(97)00453-3.
Synaptic vesicle recycling is a critical feature of neuronal communication as it ensures a constant supply of releasable transmitter at the nerve terminal. Physiological studies predict that vesicle recycling is rapid and recent studies with fluorescent dyes have confirmed that the entire process may occur in less than a minute. Two competing hypotheses have been proposed for the first step in the process comprising endocytosis of vesicular membrane. The coated vesicle model proposes that vesicular membrane components merge with the plasma membrane and are subsequently recovered and possibly sorted in coated pits. These pinch off as coated vesicles that either fuse with a sorting endosome from which new vesicles emerge or uncoat to become synaptic vesicles directly. The alternative "kiss-and-run" model proposes that "empty" vesicles are retrieved intact from the plasma membrane after secretion occurs via a fusion pore; they are then immediately refilled with transmitter and re-enter the secretion-competent pool. This article summarizes the data for both models and focusses on new information that supports the kiss-and-run model. In particular, the phenomenon of rapid endocytosis, which may represent the key endocytotic step in recycling, is discussed. Rapid endocytosis has time-constants in the order of a few seconds, thus is temporally consistent with the rate of vesicle recycling. Moreover, rapid endocytosis appears to be clathrin-independent, thus does not involve the coated vesicle pathway. We present a model that accommodates both types of endocytosis, which appear to coexist in many secretory tissues including neurons. Rapid endocytosis may reflect the principal mechanism operative under normal physiological rates of stimulation while coated vesicles may come into play at higher rates of stimulation. These two processes may feed into different populations of vesicles corresponding to distinct pools defined by studies of the kinetics of transmitter release.
突触小泡循环是神经元通讯的一个关键特征，因为它确保神经末梢有持续供应的可释放递质。生理学研究预测小泡循环很快，最近使用荧光染料的研究证实整个过程可能在不到一分钟内发生。对于包括小泡膜内吞作用在内的该过程的第一步，已经提出了两种相互竞争的假说。被膜小泡模型提出，小泡膜成分与质膜融合，随后在被膜小窝中回收并可能进行分选。这些小窝 pinched off 形成被膜小泡，它们要么与新小泡从中出现的分选内体融合，要么脱被膜直接成为突触小泡。另一种“亲吻并跑”模型提出，“空”小泡在分泌通过融合孔发生后从质膜完整回收；然后它们立即重新装满递质并重新进入具备分泌能力的池。本文总结了两种模型的数据，并着重于支持“亲吻并跑”模型的新信息。特别是，讨论了快速内吞作用这一现象，它可能代表了循环中的关键内吞步骤。快速内吞作用的时间常数约为几秒，因此在时间上与小泡循环速率一致。此外，快速内吞作用似乎不依赖网格蛋白，因此不涉及被膜小泡途径。我们提出了一个容纳两种内吞作用类型的模型，这两种内吞作用似乎在包括神经元在内的许多分泌组织中共存。快速内吞作用可能反映了在正常生理刺激速率下起作用的主要机制，而被膜小泡可能在较高刺激速率下起作用。这两个过程可能进入不同的小泡群体，对应于通过递质释放动力学研究定义的不同池。 （注：原文中“pinched off”未准确翻译，暂保留英文，因为没有明确合适的中文表述）
