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The nerve growth factor receptor TrkA exists as a pre‐formed homodimer before ligand binding
Author(s) -
Shen Jianying,
Maruyama Ichiro
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.865.1
Subject(s) - trk receptor , tropomyosin receptor kinase a , receptor , low affinity nerve growth factor receptor , neurotrophin , microbiology and biotechnology , nerve growth factor , receptor tyrosine kinase , bimolecular fluorescence complementation , chemistry , biology , biochemistry , yeast
The nerve growth factor (NGF) family of neurotrophins plays a central role in the development, growth, and maintenance of the nervous system. These neurotrophins transduce their effects by interacting with two types of cell surface receptors, the Trk family of tyrosine kinase receptors, and p75 NTR . Two classes of NGF‐binding sites, high and low affinities, are present on the surface of neurons. When TrkA and p75 NTR receptors are co‐expressed, the association rate is dramatically increased, creating a new site consistent with the NGF high affinity binding site. These results suggest that the receptors interact each other prior to ligand binding. In the present study, we have analyzed the structures of the TrkA receptor for NGF by bimolecular fluorescence complementation and luciferase fragment complementation assays as well as by chemical crosslinking of the receptor expressed on the cell surface. These analyses demonstrated that before ligand binding, the majority of receptors exist as a homodimer in living cells. Using Brefeldin A, a lactone antibiotic that disassembles the Golgi apparatus and block anterograde transport of the receptors from ER to Golgi, furthermore, it has been found that TrkA homodimers are initially formed in ER before reaching to the cell surface. This work provides new insights into understanding of transmembrane signaling by TrkA receptors.