Brain-derived neurotrophic factor receptor TrkB exists as a preformed dimer in living cells

Journal of Molecular Signaling

Ichiro N Maruyama²  Jianying Shen¹ 

[1] Department of Immunology, The Bechman Research Institute of the City of Hope, Duarte, CA 91010, USA;Information Processing Biology Unit, Okinawa Institute of Science and Technology Graduate University, Okinawa 904-0495, Japan

关键词: Preformed homodimer;    Neurotrophin receptor;    Protein fragment complementation assay;    Chemical crosslinking;    BDNF;   

Others  :  803135
DOI  :  10.1186/1750-2187-7-2

 received in 2011-11-08, accepted in 2012-01-24,  发布年份 2012

【 摘 要 】

Background

Neurotrophins (NTs) and their receptors play crucial roles in the development, functions and maintenance of nervous systems. It is widely believed that NT-induced dimerization of the receptors initiates the transmembrane signaling. However, it is still controversial whether the receptor molecule has a monomeric or dimeric structure on the cell surface before its ligand binding.

Findings

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.

Conclusions

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.

【 授权许可】

   
2012 Shen and Maruyama; licensee BioMed Central Ltd.

【 图 表 】

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