The dendritic SNARE fusion machinery involved in AMPARs insertion during long-term potentiation.

Sandra Jurado

doi:10.3389/fncel.2014.00407

Abstract

Sorting endosomes carry α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-type glutamate receptors (AMPARs) from their maturation sites to their final destination at the dendritic plasma membrane through both constitutive and regulated exocytosis. Insertion of functional AMPARs into the postsynaptic membrane is essential for maintaining fast excitatory synaptic transmission and plasticity. Despite this crucial role in neuronal function, the machinery mediating the fusion of AMPAR-containing endosomes in dendrites has been largely understudied in comparison to presynaptic vesicle exocytosis. Increasing evidence suggests that similarly to neurotransmitter release, AMPARs insertion relies on the formation of a SNARE complex (soluble NSF-attachment protein receptor), whose composition in dendrites has just begun to be elucidated. This review analyzes recent findings of the fusion machinery involved in regulated AMPARs insertion and discusses how dendritic exocytosis and AMPARs lateral diffusion may work together to support synaptic plasticity.

Highlights

As integral membrane proteins, synaptic α-amino-3-hydroxy-5methyl-4-isoxazolepropionic acid receptors (AMPARs) make use of the entire secretory pathway to reach their final destination at the postsynaptic density (PSD) of dendritic spines
Here we primarily review data from experiments addressing the mechanism of AMPARs exocytosis during NMDAR-dependent long-term synaptic potentiation (LTP) elicited in CA3-CA1 synapses in acute hippocampal slices or by activating N-methyl-D-aspartate (NMDA) receptors (NMDARs) in cultured neurons
Further structure/function analysis replacing endogenous syntaxin-3 by a non complexin-binding mutant confirmed that syntaxin-3/complexin interaction is necessary for the function of postsynaptic SNARE complexes implicated in AMPARs exocytosis. These results suggest that postsynaptic syntaxin-3 via complexins may constitutively restrict AMPARs insertion until calcium influx reaches the postsynaptic compartment in a similar fashion to their function at presynaptic terminals (Giraudo et al, 2006; Tang et al, 2006; Huntwork and Littleton, 2007; Maximov et al, 2009; Xue et al, 2009; Yang et al, 2010)

Summary

Sandra Jurado *

Sorting endosomes carry α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)type glutamate receptors (AMPARs) from their maturation sites to their final destination at the dendritic plasma membrane through both constitutive and regulated exocytosis. Insertion of functional AMPARs into the postsynaptic membrane is essential for maintaining fast excitatory synaptic transmission and plasticity. Despite this crucial role in neuronal function, the machinery mediating the fusion of AMPAR-containing endosomes in dendrites has been largely understudied in comparison to presynaptic vesicle exocytosis. This review analyzes recent findings of the fusion machinery involved in regulated AMPARs insertion and discusses how dendritic exocytosis and AMPARs lateral diffusion may work together to support synaptic plasticity

INTRODUCTION

Postsynaptic SNARE fusion during LTP