Differences in the surface binding and endocytosis of neurotrophins by p75NTR.
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.
Saxena
Smita
S
Division of Neuropathology, Institute of Pathology, University of Bern, CH-3010 Bern, Switzerland.
Howe
Charles L
CL
Cosgaya
José M
JM
Hu
Minjie
M
Weis
Joachim
J
Krüttgen
Alex
A
D000818:Animals; D001665:Binding Sites / Q000502:physiology; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism; D019556:COS Cells; D002451:Cell Compartmentation / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D022163:Clathrin-Coated Vesicles / Q000378:metabolism; D004705:Endocytosis / Q000502:physiology*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D008024:Ligands; D020932:Nerve Growth Factor / Q000378:metabolism; D009414:Nerve Growth Factors / Q000378:metabolism*; D009420:Nervous System / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D020933:Neurotrophin 3 / Q000378:metabolism; D016716:PC12 Cells; D011485:Protein Binding / Q000502:physiology; D051381:Rats; D020800:Receptor, Nerve Growth Factor; D020917:Receptor, trkA / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism*
D019208:Brain-Derived Neurotrophic Factor; D008024:Ligands; D009414:Nerve Growth Factors; D020933:Neurotrophin 3; D020800:Receptor, Nerve Growth Factor; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA