Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10957007 | Molecular and Cellular Neuroscience | 2005 | 17 Pages |
Abstract
NGF binds to two receptors, p75NTR and TrkA. The endosomal trafficking of receptors is of emerging importance for the understanding of their signaling. We compared the endocytic trafficking of the two NGF receptors in PC12 cells. Both p75NTR and TrkA were internalized in response to NGF and colocalized with early endosomes. However, surprisingly, the subsequent endosomal trafficking paths of both NGF receptors diverged: whereas p75NTR recycled back to the surface, TrkA moved to late endosomes and underwent lysosomal degradation. By performing subcellular fractionations of NGF stimulated PC12 cells, tyrosine-phosphorylated TrkA was recovered in fractions corresponding to late endosomes. This implicates these organelles as novel endosomal NGF signaling platforms. Furthermore, the trafficking of NGF receptors could be manipulated by pharmacological means. Disrupting p75NTR recycling diminished TrkA activation in response to low concentrations of NGF, demonstrating a functional role for the recycling of p75NTR.
Keywords
EGFRpost nuclear supernatantLBPARTKMVBEEA1TGFGDNFNGFCNTFTCAGFPTransferrinPBSTFRCCVDMEMBSADulbecco's modified Eagle's mediumbovine serum albuminearly endosomal antigen 1trichloroacetic acidlysobisphosphatidic acidSDS-PAGEhomogenization buffermultivesicular bodytransforming growth factornerve growth factorGlial cell line-derived neurotrophic factorciliary neurotrophic factorPhosphate buffered salineElectron microscopygreen fluorescent proteinPNSclathrin-coated vesicletransferrin receptorReceptor Tyrosine KinaseEpidermal growth factor receptor
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Authors
Smita Saxena, Charles L. Howe, José M. Cosgaya, Pascal Steiner, Harald Hirling, Jonah R. Chan, Joachim Weis, Alex Krüttgen,