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Neurotrophins Redirect p75 NTR from a Clathrin‐Independent to a Clathrin‐Dependent Endocytic Pathway Coupled to Axonal Transport
Author(s) -
Deinhardt Katrin,
Reversi Alessandra,
Berninghausen Otto,
Hopkins Colin R.,
Schiavo Giampietro
Publication year - 2007
Publication title -
traffic
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.677
H-Index - 130
eISSN - 1600-0854
pISSN - 1398-9219
DOI - 10.1111/j.1600-0854.2007.00645.x
Subject(s) - clathrin , endocytosis , endocytic cycle , internalization , microbiology and biotechnology , biology , low affinity nerve growth factor receptor , endosome , neurotrophin , nerve growth factor , dynamin , tropomyosin receptor kinase a , neurite , axoplasmic transport , receptor , intracellular , biochemistry , in vitro
The p75 neurotrophin receptor (p75 NTR ) plays multiple roles in neuronal physiology through interactions with many ligands and coreceptors. However, its intracellular neuronal trafficking prior to and after neurotrophin activation is still poorly characterized. We have previously shown that in response to nerve growth factor (NGF), p75 NTR is retrogradely transported along the axons of motor neurons (MNs) in carriers shared with NGF, brain‐derived neurotrophic factor and the tyrosine kinase receptor TrkB. Here, we report that NGF does not enhance the internalization or degradation of p75 NTR , which undergoes a rapid dynamin‐dependent and clathrin‐independent recycling process in MNs. Instead, incubation of cells with NGF leads to the redirection of a pool of plasma membrane p75 NTR into clathrin‐coated pits. The subsequent internalization of p75 NTR via clathrin‐mediated endocytosis, as well as the activity of Rab5, are essential for the sorting of the p75 NTR ‐containing endosomes to the axonal retrograde transport pathway and for the delivery of p75 NTR to the soma. Our findings suggest that the spatial regulation of p75 NTR signalling is controlled by these ligand‐driven routes of endocytosis.