Postsynaptic SNARE Proteins: Role in Synaptic Transmission and Plasticity

Abstract

Soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) proteins mediate membrane fusion events in eukaryotic cells. Traditionally recognized as major players in regulating presynaptic neurotransmitter release, accumulative evidence over recent years has identified several SNARE proteins implicated in important postsynaptic processes such as neurotransmitter receptor trafficking and synaptic plasticity. Here we analyze the emerging data revealing this novel functional dimension for SNAREs with a focus on the molecular specialization of vesicular recycling and fusion in dendrites compared to those at axon terminals and its impact in synaptic transmission and plasticity.

Keywords: neurotransmitter receptor trafficking; postsynaptic SNARE proteins; postsynaptic exocytosis; synaptic plasticity.

Figure 1:. Functions of postsynaptic synaptobrevins.

The model summarizes some of our current knowledge of the role of postsynaptic Sybs in regulating neurotransmitter receptor trafficking. Syb-2 has been suggested to be an integral part of GABA_AR-containing vesicles and regulate basal insertion in dendritic membranes. Moreover, Syb-2 may be located at AMPAR-containing endosomes, thus participating in basal and activity-dependent exocytic events either induced by NMDAR activation or during synaptic scaling induced by retinoic acid, a type of homeostatic plasticity. In addition, Syb-1, another common isoform of Syb in the CNS, has been suggested to specifically regulate constitutive NMDAR exocytosis.

Figure 2:. Functions of postsynaptic syntaxins.

The model represents the role of different postsynaptic syntaxins in regulating neurotransmitter receptor dynamics. Despite being mostly concentrated at presynaptic terminals, Stx-1 has been suggested to play a role in regulating constitutive exocytosis of GABA_ARs, AMPARs and GluN2B-containing NMDA receptors. Interestingly, GluN2A-containing NMDARs insertion may depend on Stx-4, a non-complexin Stx isoform that also mediates AMPAR exocytosis during homeostatic plasticity. In contrast Stx-3, a complexin-binding isoform is the primary regulator of AMPAR exocytosis during NMDAR-dependent LTP. These results suggest dendritic membranes may contain microdomains enriched with different Stx isoforms which define specific regions for postsynaptic receptor exocytosis.

Figure 3:. Functions of postsynaptic SNAPs.

Schematic of the identified roles of postsynaptic SNAPs depicts membrane-bound SNAP-25 and SNAP-23 primarily involved in regulating constitutive trafficking of GABA_A, AMPA and NMDA receptors. This function suggests the existence of specific membrane microdomains enriched with these SNAPs where exocytosis may be facilitated during baseline conditions. In contrast, activity-dependent insertion (NMDAR-dependent LTP and retinoic acid-induced potentiation) depends on the activity of SNAP-47, a broadly expressed cytosolic isoform. These results suggest that calcium influx increases dendritic exocytosis by recruiting SNAP isoforms like SNAP-47 which by not being attached to the membrane may define temporary regions for fusion along the dendritic membrane. By recruiting SNAP-47, the increase in postsynaptic exocytosis demand during synaptic plasticity can be supported in the absence of specialized regions like the presynaptic active zone.