IDENTIFICATION OF A SOMATODENDRITIC TARGETING SIGNAL IN THE CYTOPLASMIC DOMAIN OF THE TRANSFERRIN RECEPTOR

Neurons are highly polarized cells that must sort proteins synthesized in the cell body for transport into the axon or the dendrites. Given the amount of lime and energy needed to deliver proteins to the distal processes, neurons must have high fidelity mechanisms that ensure pro per polarized protein trafficking. Although a variety of proteins are localized either to the somatodendritic domain or to the axon (Craig a nd Banker, 1994), the question of whether there are signal-dependent m echanisms that sort proteins to distinct neuronal domains is only begi nning to be addressed, To determine sequence requirements for the pola rized sorting of transmembrane proteins into dendrites, we expressed m utant transferrin receptors in cultured rat hippocampal neurons, using a defective herpes virus vector. Wild-type human transferrin receptor colocalized with the endogenous protein in dendritic endosomes and wa s strictly excluded from axons, despite overexpression. Polarized targ eting was abolished by deletion of cytoplasmic amino acids 7-10, 11-14 , or 19-28, but not 29-42 or 43-58. These deletions also increased the appearance of transferrin receptor on the plasma membrane, implying t hat endocytosis and dendritic targeting are mediated by overlapping si gnals and similar molecular mechanisms, In addition, we have character ized a specialized para-Golgi endosome poised to play a critical role in the polarized recycling of transmembrane proteins.