Our results demonstrate that axon-dendrite and apical-basolateral sorting pathways can coexist in a single cell, and suggest that subtle changes to short sequence motifs are sufficient to redirect proteins between these pathways.Ī cell presents many faces to the world: for example, the outward-facing (apical) surface of an epithelial cell is decorated with transmembrane proteins that are different from those on its inward-facing (basolateral) surface, reflecting the specialized functions of each compartment. Indeed, changing only 2 residues in a short motif is sufficient to redirect the protein between apical, basolateral, and axonal localization. Disrupting key residues in either sequence leads to apical localization, while “improving” them to match epithelial sorting motifs leads to axon-only localization. The Tyr-based motif is conserved in human L1CAM but had not previously been assigned a function. Basolateral localization can be fully recapitulated using either of 2 short (10-aa or 19-aa) tail sequences that, respectively, resemble dileucine and Tyr-based motifs known to mediate sorting in mammalian epithelia. Using minimal synthetic transmembrane proteins, we found that the 91-aa cytoplasmic tail of SAX-7 is necessary and sufficient to direct basolateral localization. To determine how proteins are sorted among these compartments, we studied the localization of the conserved adhesion molecule SAX-7/L1CAM. The distal ∼5–10 µm of the dendrite is apical, while the remainder of the dendrite, soma, and axon are basolateral. Here, we show that Caenorhabditis elegans amphid neurons simultaneously exhibit axon-dendrite sorting like a neuron and apical-basolateral sorting like an epithelial cell. Interestingly, many sensory cells-including vertebrate photoreceptors and olfactory neurons-exhibit both neuronal and epithelial features. For example, membrane proteins are localized to axons or dendrites in neurons and to apical or basolateral surfaces in epithelial cells. Cells are highly organized machines with functionally specialized compartments.
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