title: Nerve growth factor receptor TrkA exists as a preformed, yet inactive, dimer in living cells.
abstract: The tropomyosin-related kinase A (TrkA) receptor and its ligand, nerve growth factor (NGF), play crucial roles in the development and function of the nervous system. NGF is believed to activate TrkA by bridging two TrkA monomers, leading to TrkA transphosphorylation. However, here we show that the majority of TrkA receptors exist as preformed, yet inactive, homodimers prior to NGF binding by using three different approaches such as chemical crosslinking and enzyme fragment complementation assay. Furthermore, TrkA homodimers are formed in endoplasmic reticulum before newly synthesized receptors reach the cell surface. These findings shed light on molecular mechanisms underlying transmembrane signaling by TrkA.
authors.affiliation: Information Processing Biology Unit, Okinawa Institute of Science and Technology, Okinawa, Japan.
authors.forename: Jianying
authors.initials: J
authors.lastname: Shen
authors.forename: Ichiro N
authors.initials: IN
authors.lastname: Maruyama
mesh_terms: D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D020932:Nerve Growth Factor / Q000378:metabolism; D055503:Protein Multimerization; D021381:Protein Transport; D051381:Rats; D020917:Receptor, trkA / Q000737:chemistry / Q000378:metabolism*; D017475:Receptors, Nerve Growth Factor / Q000378:metabolism
chemical_list: D017475:Receptors, Nerve Growth Factor; D020932:Nerve Growth Factor; D020917:Receptor, trkA