Article: article from journal or magazin.
Expression and function of SNAP-25 as a universal SNARE component in GABAergic neurons.
The Journal of neuroscience : the official journal of the Society for Neuroscience
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
Publication Status: ppublish
Publication Status: ppublish
Intracellular vesicular trafficking and membrane fusion are important processes for nervous system development and for the function of neural circuits. Synaptosomal-associated protein 25 kDa (SNAP-25) is a component of neural soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) core complexes that mediate the exocytotic release of neurotransmitters at chemical synapses. Previous results from mouse mutant models and pharmacological/neurotoxin blockades have demonstrated a critical role for SNAP-25-containing SNARE complexes in action potential (AP)-dependent release at cholinergic and glutamatergic synapses and for calcium-triggered catecholamine release from chromaffin cells. To examine whether SNAP-25 participates in the evoked release of other neurotransmitters, we investigated the expression and function of SNAP-25 in GABAergic terminals. Patch-clamp recordings in fetal Snap25-null mutant cortex demonstrated that ablation of SNAP-25 eliminated evoked GABA(A) receptor-mediated postsynaptic responses while leaving a low level of spontaneous AP-independent events intact, supporting the involvement of SNAP-25 in the regulated synaptic transmission of early developing GABAergic neurons. In hippocampal cell cultures of wild-type mice, punctate staining of SNAP-25 colocalized with both GABAergic and glutamatergic synaptic markers, whereas stimulus-evoked vesicular recycling was abolished at terminals of both transmitter phenotypes in Snap25-/- neurons. Moreover, immunohistochemistry and fluorescence in situ hybridization revealed coexpression of SNAP-25, VGAT (vesicular GABA transporter), and GAD65/67 (glutamic acid decarboxylase 65/67) in interneurons within several regions of the adult brain. Our results thus provide evidence that SNAP-25 is critical for evoked GABA release during development and is expressed in the presynaptic terminals of mature GABAergic neurons, consistent with its function as a component of a fundamental core SNARE complex required for stimulus-driven neurotransmission.
Animals, Cells, Cultured, Exocytosis/physiology, Gene Expression Regulation, Developmental/physiology, Hippocampus/embryology, Hippocampus/metabolism, Mice, Mice, Knockout, Neurons/metabolism, SNARE Proteins/metabolism, Synaptic Transmission/physiology, Synaptosomal-Associated Protein 25/genetics, Synaptosomal-Associated Protein 25/metabolism, gamma-Aminobutyric Acid/metabolism
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