Endocytic machinery at the neuronal synapse

Abstract

Neurotransmission, a quantal process that conveys signals from one nerve cell to another, forms the basis of intercellular communication in nervous and sensory systems. Even at modest levels of neuronal activity, the hundreds of synaptic vesicles typically present at each synapse would be rapidly used up in the absence of equally robust mechanisms that form new synaptic vesicles. Thus, normal physiology of neuronal synapses is critically dependent on synaptic vesicle recycling. However, 40 years after Heuser and Reese showed that the synaptic vesicles are locally formed and recycled at the presynaptic terminal, the precise mechanism(s) of synaptic vesicle recycling remain(s) elusive. A major role in this process is thought to be played by clathrin-mediated endocytosis, a form of endocytosis that utilizes the clathrin coat, the GTPase dynamin, and a variety of accessory factors. The contribution of two other types of endocytosis, kiss-and-run and bulk endocytosis, to the regeneration of new synaptic vesicles is still an open question. This chapter summarizes current knowledge on endocytic modes and their machinery at the presynaptic terminals, with a strong emphasis on clathrinmediated endocytosis as the predominant pathway of synaptic vesicle recycling. Given the essential nature of this topic, future progress in this field will not only advance our understanding of synaptic transmission but also have wide implications for neurophysiology, pharmacology, and medicine.