Nerve growth factor signaling in caveolae-like domains at the plasma membrane.
Publication/Presentation Date
12-17-1999
Abstract
Nerve growth factor (NGF) binding to its receptors TrkA and p75(NTR) enhances the survival, differentiation, and maintenance of neurons. Recent studies have suggested that NGF receptor activation may occur in caveolae or caveolae-like membranes (CLM). This is an intriguing possibility because caveolae have been shown to contain many of the signaling intermediates in the TrkA signaling cascade. To examine the membrane localization of TrkA and p75(NTR), we isolated caveolae from 3T3-TrkA-p75 cells and CLM from PC12 cells. Immunoblot analysis showed that TrkA and p75(NTR) were enriched about 13- and 25-fold, respectively, in caveolae and CLM. Binding and cross-linking studies demonstrated that the NGF binding to both TrkA and p75(NTR) was considerably enriched in CLM and that about 90% of high affinity binding to TrkA was present in CLM. When PC12 cells were treated with NGF, virtually all activated (i.e. tyrosine phosphorylated) TrkA was found in the CLM. Remarkably, in NGF-treated cells, it was only in CLM that activated TrkA was coimmunoprecipitated with phosphorylated Shc and PLCgamma. These results document a signaling role for TrkA in CLM and suggest that both TrkA and p75(NTR) signaling are initiated from these membranes.
Volume
274
Issue
51
First Page
36707
Last Page
36714
ISSN
0021-9258
Published In/Presented At
Huang, C. S., Zhou, J., Feng, A. K., Lynch, C. C., Klumperman, J., DeArmond, S. J., & Mobley, W. C. (1999). Nerve growth factor signaling in caveolae-like domains at the plasma membrane. The Journal of biological chemistry, 274(51), 36707–36714. https://doi.org/10.1074/jbc.274.51.36707
Disciplines
Medicine and Health Sciences | Pediatrics
PubMedID
10593976
Department(s)
Department of Pediatrics
Document Type
Article