Abstract
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Highlights
Synaptophysin 1 and 2 and synaptogyrin 1 and 3 constitute a major family of synaptic vesicle membrane proteins expressed widely, possibly in all synaptic vesicles throughout the animal kingdom (Jahn et al, 1985; Stenius, 1995; Fernandez-Chacon and Sudhof, 1999; Takamori et al, 2006)
Elevated neurotransmitter release at calyx of Held synapses from quadruple knockout mice (QKO) mice In a first set of experiments to determine the primary functional deficit, we found that calyx of Held synapses from QKO mice were substantially stronger than WT when action potentials were evoked in the afferent axon at low frequency (Figure 2A–B)
To confirm that synaptic vesicle exocytosis is increased at QKO hippocampal synapses when action potentials are fired at low frequency, and to assess the contribution of each of the four synaptophysin family members, we developed an optical imaging assay in primary cell culture with higher throughput than the electrophysiological assays
Summary
Synaptophysin 1 and 2 and synaptogyrin 1 and 3 constitute a major family of synaptic vesicle membrane proteins expressed widely, possibly in all synaptic vesicles throughout the animal kingdom (Jahn et al, 1985; Stenius, 1995; Fernandez-Chacon and Sudhof, 1999; Takamori et al, 2006). The widespread expression of neuronal family members suggests a fundamental role in synaptic transmission, but what that might be is not known. The hypothesis that the native function might involve negative regulation of exocytosis has not been pursued extensively, possibly because no clear evidence was found for increases in neurotransmitter release at synapses from synaptophysin 1 and synaptogyrin 1 single and double knockouts (McMahon et al, 1996; Janz et al, 1999; Abraham et al, 2006; Stevens et al, 2012).
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