title: Vesicle recycling revisited: rapid endocytosis may be the first step.
abstract: 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.
authors.affiliation: Department of Pharmacological and Physiological Sciences, University of Chicago, IL 60637, USA.
authors.forename: H C
authors.initials: HC
authors.lastname: Palfrey
authors.forename: C R
authors.initials: CR
authors.lastname: Artalejo
mesh_terms: D000313:Adrenal Medulla / Q000502:physiology; D000818:Animals; D002450:Cell Communication; D019439:Chromaffin Cells / Q000502:physiology; D003034:Coated Pits, Cell-Membrane / Q000502:physiology; D004705:Endocytosis; D005089:Exocytosis; D009411:Nerve Endings / Q000502:physiology; D009474:Neurons / Q000502:physiology*; D013572:Synaptic Vesicles / Q000502:physiology*