title: Actinin-1 binds to the C-terminus of A2B adenosine receptor (A2BAR) and enhances A2BAR cell-surface expression.
abstract: A2BAR (A2B adenosine receptor) has been implicated in several physiological conditions, such as allergic or inflammatory disorders, vasodilation, cell growth and epithelial electrolyte secretion. For mediating the protein-protein interactions of A2BAR, the receptor's C-terminus is recognized to be crucial. In the present study, we unexpectedly found that two point mutations in the A2BAR C-terminus (F297A and R298A) drastically impaired the expression of A2BAR protein by accelerating its degradation. Thus we tested the hypothesis that these two point mutations disrupt A2BAR's interaction with a protein essential for A2BAR stability. Our results show that both mutations disrupted the interaction of A2BAR with actinin-1, an actin-associated protein. Furthermore, actinin-1 binding stabilized the global and cell-surface expression of A2BAR. By contrast, actinin-4, another non-muscle actinin isoform, did not bind to A2BAR. Thus our findings reveal a previously unidentified regulatory mechanism of A2BAR abundance.
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.
authors.forename: Wenbao
authors.initials: W
authors.lastname: Hu
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.
authors.forename: Xiaojie
authors.initials: X
authors.lastname: Yu
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China.
authors.forename: Zhengzhao
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Cystic Fibrosis/Pulmonary Research and Treatment Center, The University of North Carolina at Chapel Hill, Chapel Hill, NC, U.S.A.
authors.forename: Robert
authors.initials: R
authors.lastname: Tarran
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA 02118, U.S.A. Department of Biochemistry, Boston University School of Medicine, Boston, MA 02118, U.S.A. Whitaker Cardiovascular Institute, Boston University School of Medicine, Boston, MA 02118, U.S.A.
authors.forename: Katya
authors.initials: K
authors.lastname: Ravid
authors.affiliation: Division of Life Science, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China Division of Biomedical Engineering, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China State Key Laboratory of Molecular Neuroscience, Hong Kong University of Science and Technology, Hong Kong, People's Republic of China bohuangp@ust.hk.
authors.forename: Pingbo
authors.initials: P
authors.lastname: Huang
mesh_terms: D000185:Actinin / Q000378:metabolism*; D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D000242:Cyclic AMP / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D047468:Immunoprecipitation; D017354:Point Mutation / Q000235:genetics; D011485:Protein Binding / Q000235:genetics / Q000502:physiology; D043704:Receptor, Adenosine A2B / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D043704:Receptor, Adenosine A2B; D000185:Actinin; D000242:Cyclic AMP
keywords: A2B adenosine receptor; G-protein-coupled receptor (GPCR); actinin; stabilization; surface expression