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.

1 Bookmark
  • [Show abstract] [Hide abstract]
    ABSTRACT: Synaptic communication in the nervous system is initiated by the fusion of synaptic vesicles with the presynaptic plasma membrane and subsequent neurotransmitter release. In the 1980s, this process was characterized by electron microscopy, albeit without the ability to follow processes in living cells. In the last two decades, fluorescence imaging methods have been developed that report synaptic vesicle fusion, endocytosis and recycling. These probes have provided unprecedented insight into synaptic vesicle trafficking in individual synaptic terminals and revealed heterogeneity in recycling pathways as well as synaptic vesicle populations. These methods either take advantage of uptake of fluorescent probes into recycling vesicles or exogenous expression of synaptic vesicle proteins tagged with a pH-sensitive fluorescent marker at regions facing the vesicle lumen. We provide an overview of these methods, with particular emphasis on the challenges associated with their use and the opportunities for future investigations.
    Nature Neuroscience 01/2014; 17(1):10-6. · 15.25 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The model genetic organism Drosophila melanogaster, commonly known as the fruit fly, uses many of the same neurotransmitters as mammals and very similar mechanisms of neurotransmitter storage, release and recycling. This system offers a variety of powerful molecular-genetic methods for the study of transporters, many of which would be difficult in mammalian models. We review here progress made using Drosophila to understand the function and regulation of neurotransmitter transporters and discuss future directions for its use.
    Neurochemistry International 04/2014; · 2.66 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Two syntaxin 1 (STX1) isoforms, HPC-1/STX1A and STX1B, are coexpressed in neurons and function as neuronal target membrane (t)-SNAREs. However, little is known about their functional differences in synaptic transmission. STX1A null mutant mice develop normally and do not show abnormalities in fast synaptic transmission, but monoaminergic transmissions are impaired. In the present study, we found that STX1B null mutant mice died within 2 weeks of birth. To examine functional differences between STX1A and 1B, we analyzed the presynaptic properties of glutamatergic and GABAergic synapses in STX1B null mutant and STX1A/1B double null mutant mice. We found that the frequency of spontaneous quantal release was lower and the paired-pulse ratio of evoked postsynaptic currents was significantly greater in glutamatergic and GABAergic synapses of STX1B null neurons. Deletion of STX1B also accelerated synaptic vesicle turnover in glutamatergic synapses and decreased the size of the readily releasable pool in glutamatergic and GABAergic synapses. Moreover, STX1A/1B double null neurons showed reduced and asynchronous evoked synaptic vesicle release in glutamatergic and GABAergic synapses. Our results suggest that although STX1A and 1B share a basic function as neuronal t-SNAREs, STX1B but not STX1A is necessary for the regulation of spontaneous and evoked synaptic vesicle exocytosis in fast transmission.
    PLoS ONE 01/2014; 9(2):e90004. · 3.73 Impact Factor

Full-text (3 Sources)

Available from
May 27, 2014