%0 Journal Article
%T Brain-derived neurotrophic factor receptor TrkB exists as a preformed dimer in living cells
%A Jianying Shen
%A Ichiro N Maruyama
%J Journal of Molecular Signaling
%D 2012
%I Ubiquity Press
%R 10.1186/1750-2187-7-2
%X Using chemical cross-linking, bimolecular fluorescence complementation (BiFC) and luciferase fragment complementation (LFC) assays, in this study, we show the brain-derived neurotrophic factor (BDNF) receptor TrkB exists as a homodimer before ligand binding. We have also found by using BiFC and LFC that the dimer forms in the endoplasmic reticulum (ER), and that the receptor lacking its intracellular domain cannot form the dimeric structure.Most, if not all, of the TrkB receptor has a preformed, yet inactive, homodimeric structure before BDNF binding. The intracellular domain of TrkB plays a crucial role in the spontaneous dimerization of the newly synthesized receptors, which occurs in ER. These findings provide new insight into an understanding of a molecular mechanism underlying transmembrane signaling mediated by NT receptors.The neurotrophin (NT) receptor family consists of the tropomyosin-related kinase receptors (Trk) A, B and C, and p75TNR, a member of the tumor necrosis factor (TNF) receptor superfamily. TrkA preferentially interacts with the nerve growth factor (NGF), TrkB with BDNF and NT-4/5, and TrkC with NT-3. NT-3 can also interact with TrkA and TrkB with relatively low affinity, and all the NTs can bind p75NTR with low affinity [1,2]. The Trk receptor kinases play crucial roles in the development and maintenance of the central and peripheral nervous system, and consist of an extracellular ligand-binding domain, a single transmembrane domain and an intracellular tyrosine kinase domain. Upon activation, the receptor kinases initiate downstream signaling cascades mediated by Ras/Raf/MAP kinase, PI3K/Akt and PLC-¦Ã [2-4]. TrkB and its ligand BDNF are highly expressed in biologically unfavourable neuroblastomas, and TrkB expression is associated with drug resistance and expression of angiogenic factors [5].It is widely believed that the Trk receptor kinases are activated through NT-induced receptor dimerization. Because the NT exists in solution as a stabl
%K BDNF
%K Chemical crosslinking
%K Protein fragment complementation assay
%K Neurotrophin receptor
%K Preformed homodimer
%U http://www.jmolecularsignaling.com/content/7/1/2