Cell
Volume 141, Issue 3, 30 April 2010, Pages 524-535
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Article
Syntaxin-4 Defines a Domain for Activity-Dependent Exocytosis in Dendritic Spines

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Summary

Changes in postsynaptic membrane composition underlie many forms of learning-related synaptic plasticity in the brain. At excitatory glutamatergic synapses, fusion of intracellular vesicles at or near the postsynaptic plasma membrane is critical for dendritic spine morphology, retrograde synaptic signaling, and long-term synaptic plasticity. Whereas the molecular machinery for exocytosis in presynaptic terminals has been defined in detail, little is known about the location, kinetics, regulation, or molecules involved in postsynaptic exocytosis. Here, we show that an exocytic domain adjacent to the postsynaptic density (PSD) enables fusion of large, AMPA receptor-containing recycling compartments during elevated synaptic activity. Exocytosis occurs at microdomains enriched in the plasma membrane t-SNARE syntaxin 4 (Stx4), and disruption of Stx4 impairs both spine exocytosis and long-term potentiation (LTP) at hippocampal synapses. Thus, Stx4 defines an exocytic zone that directs membrane fusion for postsynaptic plasticity, revealing a novel specialization for local membrane traffic in dendritic spines.

Highlights

► Activity triggers exocytosis of AMPAR-containing endosomes in dendritic spines ► Recycling endosomes fuse with the spine membrane lateral to the postsynaptic density ► The plasma membrane t-SNARE syntaxin-4 mediates spine exocytosis ► Disrupting syntaxin-4 blocks spine exocytosis and synaptic potentiation

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