Figure 1. Model of polarized trafficking in neurons.

Membrane proteins can be sorted to axon vs. dendrites by three major pathways: 1) direct polarized delivery from the trans-golgi network (TGN), 2) non-polarized delivery followed by selective retrieval and retention, 3) indirect polarized delivery via endosomes (transcytosis). In the first pathway (1) axonal and somatodendritic proteins are sorted in TGN into axonally- and somatodendritically-targeted secretory vesicles. Those vesicles are transported and fuse with axonal and somatodendritic membranes, respectively. Some evidence, coming from epithelial cells studies, suggests that cargo, which exit TGN might enter endosomes without prior appearance on the plasma membrane, which would implicate the involvement of endosomes in secretory pathway. In the second pathway (2) axonal and somatodendritic cargo exits TGN into secretory vesicles, which can fuse with both somatodendritic and axonal membranes. After this initial non-polarized insertion, proper polarized distribution of proteins is achieved by subsequent endocytic removal of missorted proteins (presumably for degradation) and retention of the properly targeted proteins at the plasma membrane. In the third pathway (3) proteins coming out of TGN are sorted into somatodendritically-targeted secretory vesicles, and then inserted into somatodendritic membrane and subsequently endocytosed into axonally-targeted endosomal compartments, which finally fuse with axonal membrane.