Journal
NEURON
Volume 53, Issue 1, Pages 25-38Publisher
CELL PRESS
DOI: 10.1016/j.neuron.2006.09.034
Keywords
-
Categories
Funding
- NIA NIH HHS [AG024987, AG020961, AG009521] Funding Source: Medline
- NIBIB NIH HHS [EB005011] Funding Source: Medline
- NICHD NIH HHS [HD018179] Funding Source: Medline
Ask authors/readers for more resources
Nerve growth factor engages two structurally distinct transmembrane receptors, TrkA and p75, which have been proposed to create a high-affinity NGF binding site through formation of a ternary TrkA/NGF/p75 complex. To define a structural basis for the high-affinity site, we have determined the three-dimensional structure of a complete extracellular domain of TrkA complexed with NGF. The complex reveals a crab-shaped homodimeric TrkA structure, but a mechanism for p75 coordination is not obvious. We investigated the heterodimerization of membrane-bound TrkA and p75, on intact mammalian cells, using a beta-gal proteinprotein interaction system. We find that NGF dimerizes TrkA and that p75 exists on the cell surface as a preformed oligomer that is not dissociated by NGF. We find no evidence for a direct TrkA/p75 interaction. We propose that TrkA and p75 likely communicate through convergence of downstream signaling pathways and/or shared adaptor molecules, rather than through direct extracellular interactions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available