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Related Experiment Video

Updated: Jan 26, 2026

Analysis of SNARE-mediated Membrane Fusion Using an Enzymatic Cell Fusion Assay

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Published on: October 19, 2012

SNAP-25 disease variants affect synaptic transmission by destabilizing SNARE complexes within a multimeric SNARE

Victoria Amstrup Vold¹, Jie Yang², Maiken Østergaard¹

¹Department of Neuroscience, University of Copenhagen, Blegdamsvej 3B, 2200 Copenhagen N, Denmark.

|January 24, 2026

Summary

This summary is machine-generated.

Mutations in SNAP-25 cause SNAREopathies, impacting synaptic release and neuronal development. The I192N variant severely affects survival and synaptic function, more so than I192T.

Keywords:

CP: Cell biology CP: Neuroscience SNARE assembly SNARE complex evoked release exocytosis neurodevelopmental disease neurotransmitter release optical tweezers spontaneous release synaptic transmission vesicle fusion

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Area of Science:

Neuroscience
Molecular Biology
Genetics

Background:

SNAREopathies are neurodevelopmental disorders caused by mutations in synaptic proteins.
SNAP-25 is a key component of the SNARE complex, essential for neurotransmitter release.

Purpose of the Study:

To investigate the functional consequences of two SNAP-25 variants (I192N and I192T) on synaptic transmission and neuronal health.
To elucidate the dominant-negative effects of these variants in the presence of wild-type SNAP-25.

Main Methods:

Utilized autaptic glutamatergic neurons to study synaptic release.
Assessed neuronal survival and dendritic branching.
Analyzed the impact of SNAP-25 variants on SNARE complex stability and function.

Main Results:

Both SNAP-25 variants destabilize the SNARE complex, reducing spontaneous and evoked synaptic release (I192N > I192T).
The I192N variant impairs neuronal survival and dendritic branching, unlike I192T.
I192N exhibits a strong dominant-negative effect on wild-type SNAP-25, particularly on spontaneous release.

Conclusions:

SNAP-25 variants disrupt synaptic machinery, leading to neurodevelopmental deficits.
Evoked neurotransmitter release is less susceptible to these variants, potentially due to a smaller functional subset of SNARE complexes mediating release.