Distribution of plasma membrane-associated syntaxins 1 through 4 indicates distinct trafficking functions in the synaptic layers of the mouse retina

BACKGROUND: Syntaxins 1 through 4 are SNAP receptor (SNARE) proteins that mediate vesicular trafficking to the plasma membrane. In retina, syntaxins 1 and 3 are expressed at conventional and ribbon synapses, respectively, suggesting that synaptic trafficking functions differ among syntaxin isoforms. To better understand syntaxins in synaptic signaling and trafficking, we further examined the cell- and synapse-specific expression of syntaxins 1 through 4 in the mouse retina by immunolabeling and confocal microscopy. RESULTS: Each isoform was expressed in the retina and showed a unique distribution in the synaptic layers of the retina, with little or no colocalization of isoforms. Syntaxin 1 was present in amacrine cell bodies and processes and conventional presynaptic terminals in the inner plexiform layer (IPL). Syntaxin 2 was present in amacrine cells and their processes in the IPL, but showed little colocalization with syntaxin 1 or other presynaptic markers. Syntaxin 3 was found in glutamatergic photoreceptor and bipolar cell ribbon synapses, but was absent from putative conventional glutamatergic amacrine cell synapses. Syntaxin 4 was localized to horizontal cell processes in the ribbon synaptic complexes of photoreceptor terminals and in puncta in the IPL that contacted dopaminergic and CD15-positive amacrine cells. Syntaxins 2 and 4 often were apposed to synaptic active zones labeled for bassoon. CONCLUSION: These results indicate that each syntaxin isoform has unique, non-redundant functions in synaptic signaling and trafficking. Syntaxins 1 and 3 mediate presynaptic transmitter release from conventional and ribbon synapses, respectively. Syntaxins 2 and 4 are not presynaptic and likely mediate post-synaptic trafficking.