TY - JOUR
T1 - Differential endocytic sorting of p75NTR and TrkA in response to NGF
T2 - A role for late endosomes in TrkA trafficking
AU - Saxena, Smita
AU - Howe, Charles L.
AU - Cosgaya, José M.
AU - Steiner, Pascal
AU - Hirling, Harald
AU - Chan, Jonah R.
AU - Weis, Joachim
AU - Krüttgen, Alex
N1 - Funding Information:
We would like to thank Dr. L.F. Reichardt (UCSF) for the gift of REX antibodies, Dr. W.C. Mobley (Stanford University) and Genentech (South San Francisco) for the gift of purified NGF, Dr. J. Gruenberg (University of Geneva) for the gift of LBPA antibodies and stimulating discussions, and S. Rossaint for help with graphic art. This study was supported by a grant from the Swiss National Science Foundation.
PY - 2005/3
Y1 - 2005/3
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=14644394937&partnerID=8YFLogxK
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U2 - 10.1016/j.mcn.2004.11.011
DO - 10.1016/j.mcn.2004.11.011
M3 - Article
C2 - 15737746
AN - SCOPUS:14644394937
SN - 1044-7431
VL - 28
SP - 571
EP - 587
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 3
ER -