The role of receptor oligomerization in modulating the expression and function of leukocyte adhesion-G protein-coupled receptors.
The human leukocyte adhesion-G protein-coupled receptors (GPCRs), the epidermal growth factor (EGF)-TM7 proteins, are shown here to function as homo- and hetero-oligomers. Using cell surface cross-linking, co-immunoprecipitation, and fluorescence resonance energy transfer analysis of EMR2, an EGF-TM7 receptor predominantly expressed in myeloid cells, we demonstrate that it forms dimers in a reaction mediated exclusively by the TM7 moiety. We have also identified a naturally occurring but structurally unstable EMR2 splice variant that acts as a dominant negative modulator by dimerizing with the wild type receptor and down-regulating its expression. Additionally, heterodimerization between closely related EGF-TM7 members is shown to result in the modulation of expression and ligand binding properties of the receptors. These findings suggest that receptor homo- and hetero-oligomerization play a regulatory role in modulating the expression and function of leukocyte adhesion-GPCRs.
Davies
John Q
JQ
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
Chang
Gin-Wen
GW
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
Yona
Simon
S
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
Gordon
Siamon
S
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the.
Stacey
Martin
M
Sir William Dunn School of Pathology, University of Oxford, South Parks Rd., Oxford, OX1 3RE, United Kingdom and the. Electronic address: martin.stacey@path.ox.ac.uk.
Lin
Hsi-Hsien
HH
Department of Microbiology and Immunology, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Rd., Kwei-San, Tao-Yuan, Taiwan. Electronic address: hhlin@mail.cgu.edu.tw.
D017398:Alternative Splicing; D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D019281:Dimerization; D031541:Fluorescence Resonance Energy Transfer; D006801:Humans; D007962:Leukocytes / Q000737:chemistry*; D008562:Membrane Glycoproteins / Q000032:analysis; D043562:Receptors, G-Protein-Coupled / Q000737:chemistry* / Q000502:physiology
C412456:ADGRE2 protein, human; C095004:ADGRE5 protein, human; D015703:Antigens, CD; D008562:Membrane Glycoproteins; D043562:Receptors, G-Protein-Coupled