SV2A and SV2C contain a unique synaptotagmin-binding site

Schivell, Amanda E.; Mochida, Sumiko; Kensel-Hammes, Patricia; Custer, Kenneth L.; Bajjalieh, Sandra M.

doi:10.1016/j.mcn.2004.12.011

Cited by 82 publications

(77 citation statements)

References 29 publications

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“…Decreased release probability in SV2 knock-out neurons is not attributable to altered calcium dependence of release One way SV2 might influence release probability is by altering the calcium dependence of release, perhaps via its interaction with synaptotagmin, a calcium sensor for synaptic vesicle exocytosis (Schivell et al, 1996;Lazzell et al, 2004;Schivell et al, 2005). We therefore analyzed the calcium dependence of release by evoking EPSCs at several calcium concentrations (0.5, 1, 2.5, 5, and 10 mM) with constant magnesium (1.5 mM).…”

Section: Loss Of Sv2 Decreases Initial Release Probability Without Afmentioning

confidence: 99%

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

et al. 2006

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We report a thorough analysis of neurotransmission in cultured hippocampal neurons lacking synaptic vesicle protein 2 (SV2), a membrane glycoprotein present in all vesicles that undergo regulated secretion. We found that SV2 selectively enhances low-frequency neurotransmission by priming morphologically docked vesicles. Loss of SV2 reduced initial release probability during a train of action potentials but had no effect on steady-state responses. The amount and decay rate of asynchronous release, two measures sensitive to presynaptic calcium concentrations, are not altered in SV2 knock-outs, suggesting that SV2 does not act by modulating presynaptic calcium. Normal neurotransmission could be temporarily recovered by delivering an exhaustive stimulus train. Our results indicate that SV2 primes vesicles in quiescent neurons and that SV2 function can be bypassed by an activity-dependent priming mechanism. We propose that SV2 action modulates synaptic networks by ensuring that low-frequency neurotransmission is faithfully conveyed.

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Section: Loss Of Sv2 Decreases Initial Release Probability Without Afmentioning

confidence: 99%

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

et al. 2006

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“…For example, cone terminals contain SV2A and SV2B, whereas rod terminals contain only SV2B [100]. SV2A interacts with the proposed calcium sensor, synaptotagmin, in a calcium-dependent manner, and SV2B interacts with synaptotagmin in a calcium-independent manner [101,102]. Knockout of SV2A reduces the size of the readily releasable pool of vesicles in hippocampal neurons [103].…”

Section: Synaptic Proteinsmentioning

confidence: 99%

Kinetics of Synaptic Transmission at Ribbon Synapses of Rods and Cones

Thoreson

2007

Mol Neurobiol

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The ribbon synapse is a specialized structure that allows photoreceptors to sustain the continuous release of vesicles for hours upon hours and years upon years but also respond rapidly to momentary changes in illumination. Light responses of cones are faster than those of rods and, mirroring this difference, synaptic transmission from cones is also faster than transmission from rods. This review evaluates the various factors that regulate synaptic kinetics and contribute to kinetic differences between rod and cone synapses. Presynaptically, the release of glutamate-laden synaptic vesicles is regulated by properties of the synaptic proteins involved in exocytosis, influx of calcium through calcium channels, calcium release from intracellular stores, diffusion of calcium to the release site, calcium buffering, and extrusion of calcium from the cytoplasm. The rate of vesicle replenishment also limits the ability of the synapse to follow changes in release. Post-synaptic factors include properties of glutamate receptors, dynamics of glutamate diffusion through the cleft, and glutamate uptake by glutamate transporters. Thus, multiple synaptic mechanisms help to shape the responses of second-order horizontal and bipolar cells. KeywordsPhotoreceptor; Synaptic transmission; Glutamate; Calcium; Vesicles; Retina Vision begins with the transduction of light into membrane potential changes as the result of an enzymatic cascade occurring in the outer segments of rod and cone photoreceptors [1,2]. Light-evoked membrane potential changes are modified by voltage-dependent currents in the inner segment [3] and transmitted to second order bipolar and horizontal cells by changes in release of the neurotransmitter, L-glutamate, from the synaptic terminals of both rods and cones. Because all of the visual information available to downstream retinal neurons must first pass through the photoreceptor synapse, synaptic transmission from photoreceptors has a considerable impact on visual perception. The focus of this review is on mechanisms that shape the kinetics of synaptic transmission at synapses of rods and cones. Additional information on other physiological and anatomical characteristics of photoreceptor ribbon synapses can be found in recent reviews [4][5][6]. Differences in Rod and Cone KineticsRod and cone photoreceptors are tonically depolarized in darkness with membrane potentials of −35 to −45 mV that allow continuous release of the neurotransmitter, L-glutamate. Light onset causes photoreceptors to hyperpolarize by as much as 30 mV, leading to a reduction in

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“…Moreover, the enormous glycosylation of SV2 proteins suggested that they could function as chemiosmotic stabilizers of synaptic vesicles (Scranton et al, 1993;Janz et al, 1998). Furthermore, SV2 interacts in vitro with synaptotagmin, the Ca 2ϩ sensor for exocytosis (Fernández-Chaćon et al, 2001;Sun et al, 2007), suggesting that SV2 acts by binding to synaptotagmin (Schivell et al, 1996), although the mode of interaction remains unclear (Pyle et al, 2000;Lazzell et al, 2004;Schivell et al, 2005). SV2C is the protein receptor for botulinum neurotoxin A, which blocks neurotransmitter release by cleaving SNAP-25 (Dong et al, 2006;Mahrhold et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

SV2 Renders Primed Synaptic Vesicles Competent for Ca²⁺-Induced Exocytosis

Chang¹,

Südhof²

2009

J. Neurosci.

163

184

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Synaptic vesicle protein 2 (SV2), one of the first synaptic vesicle proteins identified, is characterized by multiple transmembrane regions that exhibit homology to sugar transporters, and by a highly glycosylated intravesicular sequence. Deletion of SV2 causes postnatal lethality in mice, primarily because of fulminant epilepsy. At the cellular level, deletion of SV2 impairs neurotransmitter release, but its function is unknown, and even the exact point at which release is affected in SV2-deleted synapses remains unclear. Using electrophysiological approaches, we now examine at what step in exocytosis the deletion of SV2 impairs release. Our data demonstrate that deletion of SV2 produces a decrease in evoked synaptic responses without causing changes in mini frequency, mini amplitude, the readily releasable pool of vesicles, or the apparent Ca 2ϩ sensitivity of vesicle fusion. These findings indicate that a previously unidentified step may couple priming of synaptic vesicles to Ca 2ϩ triggering of fusion, and that SV2 acts in this step to render primed synaptic vesicles fully Ca 2ϩ responsive. To investigate the structural requirements for this function of SV2, we used rescue experiments. We demonstrate that conserved charged residues within the transmembrane regions and the intravesicular glycosylation of SV2 are required for its normal folding and trafficking. In contrast, the conserved putative synaptotagmin-binding sequence of SV2 is fully dispensable. Viewed together, these observations suggest that SV2 functions in a maturation step of primed vesicles that converts the vesicles into a Ca 2ϩ -and synaptotagmin-responsive state.

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SV2A and SV2C contain a unique synaptotagmin-binding site

Cited by 82 publications

References 29 publications

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

Kinetics of Synaptic Transmission at Ribbon Synapses of Rods and Cones

SV2 Renders Primed Synaptic Vesicles Competent for Ca²⁺-Induced Exocytosis

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SV2A and SV2C contain a unique synaptotagmin-binding site

Cited by 82 publications

References 29 publications

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

Synaptic Vesicle Protein 2 Enhances Release Probability at Quiescent Synapses

Kinetics of Synaptic Transmission at Ribbon Synapses of Rods and Cones

SV2 Renders Primed Synaptic Vesicles Competent for Ca2+-Induced Exocytosis

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SV2 Renders Primed Synaptic Vesicles Competent for Ca²⁺-Induced Exocytosis