, 1998). Exactly which of these models explains axonal exclusion
will have to be determined by higher-resolution analyses of AP-1 localization and dynamics in relation to those of cargo proteins. The role of signal-AP-1 interactions in somatodendritic sorting is not limited to hippocampal neurons but is also observed in cortical neurons (G.G.F., selleck products unpublished data). Moreover, this basic role appears to be evolutionarily conserved. Indeed, studies in C. elegans have shown that the μ1 ortholog UNC-101 is required for sorting of transmembrane proteins such as the odorant receptor ODR-10 ( Dwyer et al., 2001; Kaplan et al., 2010) and the polycystin 2 channel TRPP2 ( Bae et al., 2006) to olfactory cilia, a specialized dendritic subdomain of chemosensory neurons. C. elegans UNC-101 also plays a role in the sorting of several postsynaptic receptors to dendrites of RIA interneurons ( Margeta et al., 2009). Despite this conservation, there are important Autophagy inhibitor differences in the way that UNC-101/μ1A promotes dendritic
sorting in C. elegans and mammalian neurons. In chemosensory neurons from unc-101 mutant worms, ODR-10 is completely absent from both anterograde and retrograde dendritic vesicles ( Dwyer et al., 2001), in contrast to μ1A-deficient rat hippocampal neurons, in which dendritic transport in both directions is not affected. More strikingly, in RIA interneurons, UNC-101 localizes predominantly to the axonal compartment, suggesting a transcytotic mechanism in which postsynaptic receptors are not prevented from entering the axonal compartment but are efficiently retrieved to the soma for eventual delivery to dendrites ( Margeta et al., 2009). This is clearly distinct from rat hippocampal neurons wherein μ1A is depleted from axons and functions
to prevent transport of somatodendritic proteins to the axon ( Figure 5). These differences could be cargo below specific or due to the different anatomical organization of rat hippocampal neurons and C. elegans chemosensory and RIA neurons. Indeed, chemosensory neurons are bipolar cells, with a single dendrite that ends in a sensory cilium ( Dwyer et al., 2001), and RIA interneurons are pseudounipolar, with a single neurite that bifurcates into an axon and a dendrite ( Margeta et al., 2009). In addition to its role in epithelial cells and neurons, AP-1 is required for Nak-dependent localization of the Dlg protein to the basolateral surface of distal cells of Drosophila salivary glands ( Peng et al., 2009) and for preventing the Notch activator Sanpodo from recycling from endosomes to adherens junctions in Drosophila sensory organ precursor cells ( Benhra et al., 2011).