Differential effects of SNAP-25 deletion on Ca2+-dependent and Ca2+-independent neurotransmission

Peter Bronk, Ferenc Deák, Michael C. Wilson, Xinran Liu, Thomas C. Südhof, Ege T. Kavalali

Research output: Contribution to journalArticle

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Abstract

At the synapse, SNAP-25, along with syntaxin/HPC-1 and synaptobrevin/VAMP, forms SNARE N-ethylmaleimide-sensitive factor [soluble (NSF) attachment protein receptor] complexes that are thought to catalyze membrane fusion. Results from neuronal cultures of synaptobrevin-2 knockout (KO) mice showed that loss of synaptobrevin has a more severe effect on calcium-evoked release than on spontaneous release or on release evoked by hypertonicity. In this study, we recorded neurotransmitter release from neuronal cultures of SNAP-25 KO mice to determine whether they share this property. In neurons lacking SNAP-25, as those deficient in synaptobrevin-2, we found that ∼10-12% of calcium-independent excitatory and inhibitory neurotransmitter release persisted. However, in contrast to synaptobrevin-2 knockouts, this remaining readily releasable pool in SNAP-25-deficient synapses was virtually insensitive to calcium-dependent- evoked stimulation. Although field stimulation reliably evoked neurotransmitter release in synaptobrevin-2 KO neurons, responses were rare in neurons lacking SNAP-25, and unlike synaptobrevin-2- deficient synapses, SNAP-25-deficient synapses did not exhibit facilitation of release during high-frequency stimulation. This severe loss of evoked exocytosis was matched by a reduction, but not a complete loss, of endocytosis during evoked stimulation. Moreover, synaptic vesicle turnover probed by FM-dye uptake and release during hypertonic stimulation was relatively unaffected by the absence of SNAP-25. This last difference indicates that in contrast to synaptobrevin, SNAP-25 does not directly function in endocytosis. Together, these results suggest that SNAP-25 has a more significant role in calcium-secretion coupling than synaptobrevin-2.

Original languageEnglish (US)
Pages (from-to)794-806
Number of pages13
JournalJournal of Neurophysiology
Volume98
Issue number2
DOIs
StatePublished - Aug 2007

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Vesicle-Associated Membrane Protein 2
Synaptic Transmission
R-SNARE Proteins
Synapses
Calcium
Neurotransmitter Agents
Endocytosis
Neurons
Knockout Mice
Syntaxin 1
SNARE Proteins
Membrane Fusion
Ethylmaleimide
Synaptic Vesicles
Exocytosis
Coloring Agents

ASJC Scopus subject areas

  • Physiology
  • Neuroscience(all)

Cite this

Bronk, P., Deák, F., Wilson, M. C., Liu, X., Südhof, T. C., & Kavalali, E. T. (2007). Differential effects of SNAP-25 deletion on Ca2+-dependent and Ca2+-independent neurotransmission. Journal of Neurophysiology, 98(2), 794-806. https://doi.org/10.1152/jn.00226.2007

Differential effects of SNAP-25 deletion on Ca2+-dependent and Ca2+-independent neurotransmission. / Bronk, Peter; Deák, Ferenc; Wilson, Michael C.; Liu, Xinran; Südhof, Thomas C.; Kavalali, Ege T.

In: Journal of Neurophysiology, Vol. 98, No. 2, 08.2007, p. 794-806.

Research output: Contribution to journalArticle

Bronk, P, Deák, F, Wilson, MC, Liu, X, Südhof, TC & Kavalali, ET 2007, 'Differential effects of SNAP-25 deletion on Ca2+-dependent and Ca2+-independent neurotransmission', Journal of Neurophysiology, vol. 98, no. 2, pp. 794-806. https://doi.org/10.1152/jn.00226.2007
Bronk, Peter ; Deák, Ferenc ; Wilson, Michael C. ; Liu, Xinran ; Südhof, Thomas C. ; Kavalali, Ege T. / Differential effects of SNAP-25 deletion on Ca2+-dependent and Ca2+-independent neurotransmission. In: Journal of Neurophysiology. 2007 ; Vol. 98, No. 2. pp. 794-806.
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