Palmitoylation of the p75 neurotrophin receptor has no effect on its interaction with TrkA or on TrkA-mediated down-regulation of cell adhesion molecules.
The short- and long-term effects of nerve growth factor (NGF) were studied on fibroblast cell lines stably expressing both TrkA and either wild-type p75 or a mutant that lacks the palmitoylation site of p75. The lack of palmitoylation had no effect on the ability of p75 to enhance the short-term NGF-induced tyrosine phosphorylation of TrkA over a wide range of NGF concentrations. Long-term treatment of the cell lines with NGF led to loss of cell adhesion to the culture dishes that increased with increasing concentrations of NGF and increased expression of TrkA. Treatment of the cell lines with mutant NGFs that bound selectively to TrkA or p75 alone revealed that cell detachment was mediated solely through TrkA. Increased cell detachment correlated with a decrease in the expression levels of fibronectin and cadherin, cell surface molecules involved in cell adhesion. The loss of cell adhesion with the cell line expressing the palmitoylation-deficient p75 were identical to those expressing wild type, as was anticipated from the lack of involvement of p75 in this process.
Vesa
J
J
Department of Neurobiology, Stanford University School of Medicine, Stanford, California 94305-5125, USA.
Krüttgen
A
A
Cosgaya
J M
JM
Shooter
E M
EM
D000818:Animals; D015703:Antigens, CD / Q000187:drug effects / Q000378:metabolism*; D015815:Cell Adhesion Molecules / Q000187:drug effects / Q000378:metabolism*; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D015536:Down-Regulation; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D020932:Nerve Growth Factor / Q000494:pharmacology; D020917:Receptor, trkA / Q000187:drug effects / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000187:drug effects / Q000378:metabolism*; D047889:Receptors, Tumor Necrosis Factor, Type II
D015703:Antigens, CD; D015815:Cell Adhesion Molecules; D018124:Receptors, Tumor Necrosis Factor; D047889:Receptors, Tumor Necrosis Factor, Type II; D020932:Nerve Growth Factor; D020917:Receptor, trkA