Retinal pigment epithelial cells exhibit unique expression and localization of plasma membrane syntaxins which may contribute to their trafficking phenotype

The SNARE membrane fusion machinery controls the fusion of transport vesicles with the apical and basolateral plasma-membrane domains of epithelial cells and is implicated in the specificity of polarized trafficking. To test the hypothesis that differential expression and localization of SNAREs may be a mechanism that contributes to cell-type-specific polarity of different proteins, we studied the expression and distribution of plasma-membrane SNAREs in the retinal pigment epithelium (RPE), an epithelium in which the targeting and steady-state polarity of several plasma membrane proteins differs from most other epithelia. We show here that retinal pigment epithelial cells both in vitro and in vivo differ significantly from MDCK cells and other epithelial cells in their complement of expressed t-SNAREs that are known — or suggested — to be involved in plasma membrane trafficking. Retinal pigment epithelial cells lack expression of the normally apical-specific syntaxin 3. Instead, they express syntaxins 1A and 1B, which are normally restricted to neurons and neuroendocrine cells, on their apical plasma membrane. The polarity of syntaxin 2 is reversed in retinal pigment epithelial cells, and it localizes to a narrow band on the lateral plasma membrane adjacent to the tight junctions. In addition, syntaxin 4 and the v-SNARE endobrevin/VAMP-8 localize to this sub-tight junctional domain, which suggests that this is a region of preferred vesicle exocytosis. Altogether, these data suggest that the unique polarity of many retinal pigment epithelial proteins results from differential expression and distribution of SNAREs at the plasma membrane. We propose that regulation of the expression and subcellular localization of plasma membrane SNAREs may be a general mechanism that contributes to the establishment of distinct sorting phenotypes among epithelial cell types.