TY - JOUR
T1 - Differences in the surface binding and endocytosis of neurotrophins by p75NTR
AU - Saxena, Smita
AU - Howe, Charles L.
AU - Cosgaya, José M.
AU - Hu, Minjie
AU - Weis, Joachim
AU - Krüttgen, Alex
N1 - Funding Information:
We would like to thank Dr. W.C. Mobley (Stanford University), Dr. E.M. Shooter (Stanford University), Dr. L. F. Reichardt (UCSF), Dr. J. Chan (Stanford University), Dr. B. Barres (Stanford University), Dr. P. Barker (McGill University), and Regeneron Pharmaceuticals for reagents and/or discussions. We are grateful to Dr. A. Kappeler (University of Bern), Dr. K. Baltensperger (University of Bern), and Dr. H. Hirling (Ecole Polytechnique Fédérale de Lausanne) for advice on microscopy. Furthermore, we acknowledge the gift of iodinated neurotrophins by Dr. P. DiStefano (formerly at Regeneron Pharmaceuticals) during the initiation of this project. This study was supported by a grant from the Swiss National Science Foundation.
PY - 2004/6
Y1 - 2004/6
N2 - Neurotrophins transmit signals retrogradely from synapses to cell bodies by two different types of surface receptors, p75NTR and Trks. Compared to TrkA, the function of p75NTR in nerve growth factor (NGF) endocytosis is less clear, and it is unknown whether p75NTR by itself may internalize other neurotrophins besides NGF. We directly compared TrkA and p75NTR for their ability to internalize NGF, and we also examined the endocytosis of iodinated brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) by p75NTR. Cells expressing solely TrkA internalized NGF more efficiently than cells expressing p75NTR. Surprisingly, cells expressing only p75NTR internalized far more BDNF or NT3 than NGF. Moreover, p75NTR was more important for surface binding than for intracellular accumulation of each neurotrophin. Finally, we established a mechanistic role for the clathrin pathway in p75NTR endocytosis. Our results suggest that p75NTR may have multiple roles in different subcellular locations, functioning both at the cell surface and also within endocytic compartments.
AB - Neurotrophins transmit signals retrogradely from synapses to cell bodies by two different types of surface receptors, p75NTR and Trks. Compared to TrkA, the function of p75NTR in nerve growth factor (NGF) endocytosis is less clear, and it is unknown whether p75NTR by itself may internalize other neurotrophins besides NGF. We directly compared TrkA and p75NTR for their ability to internalize NGF, and we also examined the endocytosis of iodinated brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) by p75NTR. Cells expressing solely TrkA internalized NGF more efficiently than cells expressing p75NTR. Surprisingly, cells expressing only p75NTR internalized far more BDNF or NT3 than NGF. Moreover, p75NTR was more important for surface binding than for intracellular accumulation of each neurotrophin. Finally, we established a mechanistic role for the clathrin pathway in p75NTR endocytosis. Our results suggest that p75NTR may have multiple roles in different subcellular locations, functioning both at the cell surface and also within endocytic compartments.
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U2 - 10.1016/j.mcn.2004.02.006
DO - 10.1016/j.mcn.2004.02.006
M3 - Article
C2 - 15207854
AN - SCOPUS:2942659327
SN - 1044-7431
VL - 26
SP - 292
EP - 307
JO - Molecular and Cellular Neuroscience
JF - Molecular and Cellular Neuroscience
IS - 2
ER -