期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 32, 期 4, 页码 387-402出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2006.06.001
关键词
nerve growth factor; brain-derived neurotrophic factor; TrkB; endocytosis; caveolae; caveolin; neurotrophin; neurotrophins; clathrin
BDNF, through p75NTR, promotes apoptosis and inhibits axonal growth of sympathetic neurons, antagonizing the pro-survival and axon growth-promoting actions of NGF through TrkA. While the trafficking of the TrkA:NGF complex is well characterized, little is known about p75NTR:BDNF trafficking in these neurons. Here we show that BDNF binds to and appears inside sympathetic neurons relatively slowly, although the temperature-sensitive internalization step itself is rapid. P75NTR internalization is partially sensitive to disruption of clathrin- or raft-mediated internalization, while that of TrkA is entirely clathrin-mediated. P75NTR, but not Trk, associates with neurotrophins in lipid rafts and coimmunoprecipitates with the truncated beta-caveolin-1 isoform. Finally, we directly visualize the retrograde transport of p75NTR ligands to cell bodies, which is insensitive to inhibitors of Trk retrograde transport, suggesting mechanistic differences. We postulate that beta-caveolin-1-containing lipid rafts and possibly intracellular endosomes might be compartments to which p75NTR:BDNF complexes are trafficked separately from Trk. (c) 2006 Elsevier Inc. All rights reserved.
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