title: Uncovering multiple axonal targeting pathways in hippocampal neurons.
abstract: Neuronal polarity is, at least in part, mediated by the differential sorting of membrane proteins to distinct domains, such as axons and somata/dendrites. We investigated the pathways underlying the subcellular targeting of NgCAM, a cell adhesion molecule residing on the axonal plasma membrane. Following transport of NgCAM kinetically, surprisingly we observed a transient appearance of NgCAM on the somatodendritic plasma membrane. Down-regulation of endocytosis resulted in loss of axonal accumulation of NgCAM, indicating that the axonal localization of NgCAM was dependent on endocytosis. Our data suggest the existence of a dendrite-to-axon transcytotic pathway to achieve axonal accumulation. NgCAM mutants with a point mutation in a crucial cytoplasmic tail motif (YRSL) are unable to access the transcytotic route. Instead, they were found to travel to the axon on a direct route. Therefore, our results suggest that multiple distinct pathways operate in hippocampal neurons to achieve axonal accumulation of membrane proteins.
mesh_terms: D000818:Animals; D001369:Axons / Q000502:physiology*; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D002462:Cell Membrane / Q000502:physiology; D016764:Cell Polarity / Q000502:physiology; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology; D004705:Endocytosis / Q000502:physiology; D011992:Endosomes / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D007700:Kinetics; D009474:Neurons / Q000502:physiology* / Q000648:ultrastructure; D021382:Protein Sorting Signals / Q000502:physiology; D021381:Protein Transport / Q000502:physiology*; D051381:Rats
chemical_list: D015815:Cell Adhesion Molecules; D021382:Protein Sorting Signals