Neuronal Early Endosomes Require EHD1 for L1/NgCAM Trafficking
| Autor: | Chan Choo Yap, Steven H Caplan, Bettina Winckler, Zofia M. Lasiecka |
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| Rok vydání: | 2010 |
| Předmět: |
Neurite
Endosome Green Fluorescent Proteins Vesicular Transport Proteins Down-Regulation Nerve Tissue Proteins Endosomes Biology Transfection Endocytosis Hippocampus Models Biological Article EEA1 GTP-Binding Proteins Live cell imaging Animals RNA Small Interfering Cells Cultured Neurons Microscopy Confocal General Neuroscience Cell Adhesion Molecules Neuron-Glia Transferrin Dendrites Membrane transport Embryo Mammalian Rats Cell biology Transport protein Protein Transport nervous system Synaptic plasticity |
| Zdroj: | The Journal of Neuroscience. 30:16485-16497 |
| ISSN: | 1529-2401 0270-6474 |
| Popis: | In neurons, the endosomal system is essential for membrane receptor trafficking to dendrites and axons and thereby participates in various neuronal functions, such as neurite outgrowth and synaptic plasticity. A multitude of regulators coordinates trafficking through endosomes, but most of them have not been studied in detail in neurons. In non-neuronal cells, EHD1 (Eps15 homology-domain containing protein 1) functions in the recycling endosome and is required for endosome-to-plasma membrane transport of multiple cargos. In this study, we analyze the role of EHD1 in neurons. In particular, we investigate whether EHD1 is required for polarized trafficking of the dendritically targeted transferrin and the axonal adhesion molecule L1/NgCAM (neuron–glia cell adhesion molecule) and, if so, in what compartment it is required. We find that endosomal recycling of both L1/NgCAM and transferrin is impaired when EHD1 is downregulated. We show that EHD1 colocalizes with L1/NgCAM and transferrin mostly in EEA1 (early endosome antigen 1)-positive early endosomes and less extensively with recycling endosomes. Using live imaging, we observe that EHD1 is stably associated with endosomal membranes during their maturation into EEA1-positive compartments and often persists on them longer than EEA1. Finally, we show that downregulation of EHD1 causes a delay of L1/NgCAM in exiting EEA1-positive endosomes, resulting in impaired targeting of L1/NgCAM to the axonal membrane. We conclude that, in neurons, EHD1 functions in early endosomes rather than (or possibly in addition to) recycling endosomes. These findings point to the existence of neuronal adaptations of the endosomal system. |
| Databáze: | OpenAIRE |
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