Differential Abilities of Snap-25 Homologs to Support Neuronal Function.
From: Department of Membrane Biophysics, Max Planck Institute for Biophysical Chemistry, D-37077 Göttingen, Germany.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Aug 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 35
- Pages: 9380-91
- Medium: Internet
- Language: English
- Citation (JAMA): Delgado-Martínez Ignacio, Nehring Ralf B, Sørensen Jakob B, et al. Differential Abilities of Snap-25 Homologs to Support Neuronal Function.. J. Neurosci. Aug 2007;27:9380-91
Abstract
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.
Mesh Headings (Keywords): Alternative Splicing, Analysis of Variance, Animals, Cell Survival, Cells, Cultured, Dose-Response Relationship, Radiation, Electric Stimulation, Embryo, Mammalian, Excitatory Postsynaptic Potentials, Gene Expression Regulation, Genetic Vectors, Glutamic Acid, Hippocampus, Lentivirus, Mice, Mice, Knockout, Neurons, Patch-Clamp Techniques, Pyridinium Compounds, Synaptosomal-Associated Protein 25, gamma-Aminobutyric Acid
Check for Full Text / PubMed Unique Identifier (PMID): 17728451
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