title: Single-Molecule Imaging Demonstrates Ligand Regulation of the Oligomeric Status of CXCR4 in Living Cells.
abstract: The role of dimerization and oligomerization of G-protein-coupled receptors in their signal transduction is highly controversial. Delineating this issue can greatly facilitate rational drug design. With single-molecule imaging, we show that chemokine receptor CXCR4 exists mainly as a monomer in normal mammalian living cells and forms dimers and higher-order oligomers at a high expression level, such as in cancer cells. Chemotaxis tests demonstrate that the signal transduction activity of CXCR4 does not depend only on its expression level, indicating a close relation with the oligomeric status of CXCR4. Moreover, binding ligands can effectively upregulate or downregulate the oligomeric level of CXCR4, which suggests that binding ligands may realize their pivotal roles by regulating the oligomeric status of CXCR4 rather than by simply inducing conformational changes.
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Jun
authors.initials: J
authors.lastname: Lao
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Hua
authors.initials: H
authors.lastname: He
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Xiaojuan
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Zhencai
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Yanzhuo
authors.initials: Y
authors.lastname: Song
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Naseer
authors.initials: N
authors.lastname: Ullahkhan
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Baosheng
authors.initials: B
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Heavy Oil Processing and Center for Bioengineering and Biotechnology, China University of Petroleum (East China) , Qingdao 266580, P. R. China.
authors.forename: Fang
authors.identifier: 0000-0001-8735-0350
authors.initials: F
authors.lastname: Huang
mesh_terms: D001596:Benzylamines; D002461:Cell Line, Transformed; D045744:Cell Line, Tumor; D054377:Chemokine CXCL12 / Q000494:pharmacology; D000080027:Cyclams; D006571:Heterocyclic Compounds / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D008856:Microscopy, Fluorescence; D009842:Oligopeptides / Q000494:pharmacology; D055503:Protein Multimerization / Q000187:drug effects / Q000502:physiology*; D019718:Receptors, CXCR4 / Q000819:agonists / Q000737:chemistry / Q000378:metabolism*
chemical_list: D001596:Benzylamines; C527276:CXCR4 protein, human; D054377:Chemokine CXCL12; D000080027:Cyclams; D006571:Heterocyclic Compounds; D008024:Ligands; D009842:Oligopeptides; D019718:Receptors, CXCR4; C504129:TC14012; C088327:plerixafor