LTP requires a unique postsynaptic SNARE fusion machinery
Sandra Jurado1, Debanjan Goswami, Yingsha Zhang
1Nancy Pritzker Laboratory, Department of Psychiatry and Behavioral Sciences, Stanford University School of Medicine, 265 Campus Drive, Stanford, CA 94305, USA.
Neuron
|February 12, 2013
Summary
Activity-dependent AMPA receptor (AMPAR) exocytosis during long-term potentiation (LTP) relies on unique SNARE/SM protein machinery. Syntaxin-3 and SNAP-47 are crucial for LTP-stimulated AMPAR release, distinct from neurotransmitter release mechanisms.
Area of Science:
- Neuroscience
- Molecular Biology
- Cell Biology
Background:
- Membrane fusion in exocytosis is orchestrated by SNARE and SM protein complexes.
- While presynaptic SNARE/SM proteins are well-characterized, the machinery for postsynaptic AMPA receptor (AMPAR) exocytosis during long-term potentiation (LTP) remains largely unknown.
Purpose of the Study:
- To elucidate the specific SNARE/SM protein machinery governing activity-dependent AMPA receptor exocytosis during LTP.
- To differentiate the molecular mechanisms of regulated AMPAR exocytosis in LTP from constitutive exocytosis and presynaptic release.
Main Methods:
- Direct electrophysiological measurements of LTP in acute hippocampal slices.
- In vitro models simulating stimulated AMPAR exocytosis.
- Investigating the roles of specific Q-SNARE (syntaxin-3, SNAP-47) and R-SNARE (synaptobrevin-2/VAMP2) proteins.
Main Results:
- Syntaxin-3 and SNAP-47 are essential for regulated AMPAR exocytosis during LTP, but not for basal exocytosis.
- Synaptobrevin-2/VAMP2 participates in both regulated and constitutive AMPAR exocytosis.
- Specific binding sites on syntaxin-3 (complexin-binding and Munc18-binding) are critical for its postsynaptic function in LTP.
Conclusions:
- Postsynaptic AMPAR exocytosis during LTP is mediated by a distinct fusion machinery.
- This LTP-specific machinery differs significantly from the protein assemblies involved in presynaptic neurotransmitter release.
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