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 time and energy needed to deliver proteins to the distal processes, neurons must have high fidelity mechanisms that ensure proper polarized protein trafficking. Although a variety of proteins are localized either to the somatodendritic domain or to the axon (), the question of whether there are signal-dependent mechanisms that sort proteins to distinct neuronal domains is only beginning to be addressed. To determine sequence requirements for the polarized sorting of transmembrane proteins into dendrites, we expressed mutant 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 was strictly excluded from axons, despite overexpression. Polarized targeting 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 that endocytosis and dendritic targeting are mediated by overlapping signals and similar molecular mechanisms. In addition, we have characterized a specialized para-Golgi endosome poised to play a critical role in the polarized recycling of transmembrane proteins.
West
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AE
Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.
Neve
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RL
Buckley
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KM
D000818:Animals; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000737:chemistry / Q000378:metabolism; D003712:Dendrites / Q000737:chemistry / Q000502:physiology* / Q000648:ultrastructure; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000737:chemistry / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D016296:Mutagenesis / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D017434:Protein Structure, Tertiary; D051381:Rats; D017207:Rats, Sprague-Dawley; D011990:Receptors, Transferrin / Q000737:chemistry / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology*
D011990:Receptors, Transferrin