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The Journal of Neuroscience, August 29, 2007, 27(35):9380-9391; doi:10.1523/JNEUROSCI.5092-06.2007

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Cellular/Molecular
Differential Abilities of SNAP-25 Homologs to Support Neuronal Function

Ignacio Delgado-Martínez, Ralf B. Nehring, and Jakob B. Sørensen

Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany

Correspondence should be addressed to Jakob B. Sørensen, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077, Göttingen, Germany. Email: jsoeren{at}gwdg.de

The SNAP receptor (SNARE) complex, consisting of synaptosome-associated protein of 25 kDa (SNAP-25), synaptobrevin-2, and syntaxin-1, is involved in synaptic vesicles exocytosis. In addition, SNAP-25 has been implicated in constitutive exocytosis processes required for neurite outgrowth. However, at least three isoforms of SNAP-25 have been reported from neurons: SNAP-23, which is also present in non-neuronal cells, and the two alternative splice variants SNAP-25a and SNAP-25b. Here, we studied the differential ability of these isoforms to support the functions previously broadly ascribed to "SNAP-25." We studied the rescue of snap-25 null neurons in culture with different SNAP-25 homologs. We find that deletion of SNAP-25 leads to strongly reduced neuron survival, and, in the few surviving cells, impaired arborization, reduced spontaneous release, and complete arrest of evoked release. Lentiviral expression of SNAP-25a, SNAP-25b, or SNAP-23 rescued neuronal survival, arborization, amplitude, and frequency of spontaneous events. Also evoked release was rescued by all isoforms, but synchronous release required SNAP-25a/b in both glutamatergic and GABAergic neurons. SNAP-23 supported asynchronous release only, reminiscent of synaptotagmin-1 null neurons. SNAP-25b was superior to SNAP-25a in vesicle priming, resembling the shift to larger releasable vesicle pools that accompanies synaptic maturation. These data demonstrate a differential ability of SNAP-25b, SNAP-25a, and SNAP-23 to support neuronal function.

Key words: SNAP-25; SNAP-23; neurite outgrowth; asynchronous release; hippocampal neurons; striatal neurons

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Received Nov. 23, 2006; revised July 10, 2007; accepted July 10, 2007.

Correspondence should be addressed to Jakob B. Sørensen, Max Planck Institute for Biophysical Chemistry, Am Fassberg 11, D-37077, Göttingen, Germany. Email: jsoeren{at}gwdg.de

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