Article

v-SNARE composition distinguishes synaptic vesicle pools.

Department of Neurology, University of California, San Francisco School of Medicine, San Francisco, CA 94143, USA.
Neuron (Impact Factor: 15.77). 08/2011; 71(3):474-87. DOI: 10.1016/j.neuron.2011.06.010
Source: PubMed

ABSTRACT Synaptic vesicles belong to two distinct pools, a recycling pool responsible for the evoked release of neurotransmitter and a resting pool unresponsive to stimulation. The uniform appearance of synaptic vesicles has suggested that differences in location or cytoskeletal association account for these differences in function. We now find that the v-SNARE tetanus toxin-insensitive vesicle-associated membrane protein (VAMP7) differs from other synaptic vesicle proteins in its distribution to the two pools, providing evidence that they differ in molecular composition. We also find that both resting and recycling pools undergo spontaneous release, and when activated by deletion of the longin domain, VAMP7 influences the properties of release. Further, the endocytosis that follows evoked and spontaneous release differs in mechanism, and specific sequences confer targeting to the different vesicle pools. The results suggest that different endocytic mechanisms generate synaptic vesicles with different proteins that can endow the vesicles with distinct properties.

Full-text

Available from: Sergio Leal-Ortiz, Mar 31, 2015

Click to see the full-text of:

Article: v-SNARE composition distinguishes synaptic vesicle pools.

2.49 MB

See full-text
1 Bookmark
 · 
155 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: The ability of synapses to sustain neurotransmitter release during continuous activity critically relies on an efficient vesicle recycling program. Despite extensive research on synaptic function, the basic mechanisms of vesicle recycling remain poorly understood due to the relative inaccessibility of central synapses to conventional recording techniques. The extremely small size of synaptic vesicles, nearly five times below the diffraction-limited resolution of conventional light microscopy, has hampered efforts to define the mechanisms controlling their cycling. The complex sequence of dynamic processes that occur within the nerve terminals and link vesicle endocytosis and the subsequent round of release has been particularly difficult to study. The recent development of nanoscale-resolution imaging techniques has provided an opportunity to overcome these limitations and begin to reveal the mechanisms controlling vesicle recycling within individual nerve terminals. Here we summarize the recent advances in the implementation of super-resolution imaging and single-particle tracking approaches to study the dynamic steps of the vesicle recycling process within presynaptic terminals. This article is protected by copyright. All rights reserved.
    Synapse 12/2014; DOI:10.1002/syn.21795 · 2.43 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The function of the nervous system depends on the exocytotic release of neurotransmitter from synaptic ves-icles (SVs). To sustain neurotransmission, SV membranes need to be retrieved, and SVs have to be reformed locally within presynaptic nerve terminals. In spite of more than 40 years of research, the mechanisms under-lying presynaptic membrane retrieval and SV recycling remain controversial. Here, we review the current state of knowledge in the field, focusing on the molecular mechanism involved in presynaptic membrane retrieval and SV reformation. We discuss the challenges associated with studying these pathways and pre-sent perspectives for future research. Introduction Communication within the nervous system relies on the release of neurotransmitter by the calcium-triggered fusion of synaptic vesicles (SVs) with the presynaptic plasma membrane at the nerve terminal. The number of vesicles available for fusion and their propensity to undergo exocytosis define the efficacy of neurotransmitter release and fine-tune neuronal function. Given the distance of the presynaptic terminal from the neuronal cell body the replacement of fused SVs by de novo synthesis and axonal transport would be far too slow (on the timescale of hours to days) to sustain neuronal activity. In addition, the continuous fusion of SVs with the plasma membrane in the absence of compensatory membrane retrieval would cause a detrimental in-crease in the area of the presynaptic plasma membrane, loss of membrane tension, and the misalignment with postsynaptic structures. Hence, neurons have evolved mechanisms to main-tain presynaptic membrane homeostasis by recycling SV mem-branes locally within their nerve terminals. This specific property of SVs to undergo a local trafficking cycle has drawn the atten-tion of neuroscientists for more than 40 years, but in spite of its importance for synaptic transmission, the precise mechanisms by which exocytosed SV membranes are recycled and SVs are reformed remain enigmatic.
    Neuron 02/2015; 85(3):484-496. DOI:10.1016/j.neuron.2014.12.016 · 15.77 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Fast synaptic communication in the brain requires synchronous vesicle fusion that is evoked by action potential-induced Ca(2+) influx. However, synaptic terminals also release neurotransmitters by spontaneous vesicle fusion, which is independent of presynaptic action potentials. A functional role for spontaneous neurotransmitter release events in the regulation of synaptic plasticity and homeostasis, as well as the regulation of certain behaviours, has been reported. In addition, there is evidence that the presynaptic mechanisms underlying spontaneous release of neurotransmitters and their postsynaptic targets are segregated from those of evoked neurotransmission. These findings challenge current assumptions about neuronal signalling and neurotransmission, as they indicate that spontaneous neurotransmission has an autonomous role in interneuronal communication that is distinct from that of evoked release.
    Nature reviews. Neuroscience 12/2014; 16(1):5-16. DOI:10.1038/nrn3875 · 31.38 Impact Factor