![]() ![]() Polarity, trafficking, axon-dendrite, apical-basolateral, Caenorhabditis elegans, sensory cells IntroductionĪ 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. 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. 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. 436:704–707.Cells are highly organized machines with functionally specialized compartments. Given the centrosome's ability to polarize membrane growth, Dotti wonders whether its rotation within the cell is actually required to make the later, dendrite-forming neurites.ĭe Anda, F.C., et al. Loss of centrosomal function, in contrast, blocked axon formation and led only to dendrites.Not long after mitosis, the centrosome changes its position, so it is easy to imagine why scientists have missed the centrosome–axon correlation. Cells with two centrosomes-and therefore two early neurites-formed two axons. The first neurite is expected to receive the most external growth cues, given a uniform environment, and thus would be the first to reach any threshold that leads to axon commitment. Or it might be due to the local destabilization of actin filaments (which promotes membrane fusion events) by pericentrosomal proteins. This polarization might be a result of mechanical deformation of the membrane by centrosome-organized microtubules (perhaps as a continuation of cytokinetic forces). Polarized membrane trafficking was aimed at the plasma membrane near the centrosome. It was here, near the centrosome, where the first lamellipod (and thus the first neurite) formed. “To find the specific molecular events that are instructions for polarity,” says Dotti, “we should look at the immediate postmitotic stage, even before neurites form.”Īt this stage, the centrosome and Golgi apparatus still sit on the opposite end of the cell from the site of cytokinesis. No one has seen this association before because they have been looking at stage 2 neurons, which have already formed many neurites. The centrosome (green), which sits opposite the division plane (dotted line), determines where the axon forms.īy the time the first neurite forms, the group finds, it already marks the location of the axon. ![]()
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