Seven transmembrane receptors, of which most are G protein-coupled receptors, form the largest class of membrane proteins in humans. These receptors are essential in human physiology, play major roles in a broad variety of disease processes and are the targets of more than one third of all drugs approved by the Federal Drug Administration. Since several years, our research is focused on the roles of heteromeric G protein-coupled receptor complexes in the regulation of organ and cell function in health and disease processes. Our more recent studies revealed that chemokine (C-X-C motif) receptor 4 and atypical chemokine receptor 3 regulate α1-adrenergic receptors, arginine vasopressin receptor 1A and protease activated receptor 1 through the formation of hetero-oligomeric receptor complexes. These newly discovered receptor interactions appear to be important for the regulation of blood pressure control, the development and prevention of acute respiratory distress syndrome and the regulation of leukocyte trafficking and function during sterile and infectious inflammation. We are currently studying the assembly, regulation and function of higher-order hetero-oligomeric receptor complexes on the molecular level and pursue novel strategies to utilize these receptor complexes as drug targets in disease processes.

Gao X, Cheng YH, Enten GA, DeSantis AJ, Gaponenko V, Majetschak M. Regulation of the thrombin/protease-activated receptor 1 axis by chemokine (C-X-C motif) receptor 4. J. Biol. Chem. published online August 24, 2020. doi:10.1074/jbc.RA120.015355

Gao X, Enten GA, DeSantis AJ, Volkman BF, Gaponenko V, Majetschak M. Characterization of heteromeric complexes between chemokine (C-X-C motif) receptor 4 and 1-adrenergic receptors utilizing intermolecular bioluminescence resonance energy transfer assays. Biochem Biophys Res Commun., 2020 Jul 23;528(2):368-375. doi: 10.1016/j.bbrc.2020.02.094. Epub 2020 Feb 19.

Babu FS, Liang X, Enten GA, DeSantis AJ, Volkman BF, Gao X, Majetschak M. Therapeutic potential of natural and engineered chemokine (C-X-C motif) receptor 4 agonists for trauma and hemorrhage-induced acute respiratory distress syndrome. Sci Rep., 2020 Jul 9;10(1):11359. doi: 10.1038/s41598-020-68425-0.

Gao X, Albee LJ, Volkman BF, Gaponenko V, Majetschak M. Asymmetrical ligand-induced cross-regulation of chemokine (C-X-C motif) receptor 4 by α1-adrenergic receptors at the heteromeric receptor complex. Sci Rep. 2018 Feb 9;8(1):2730.

Albee LJ, LaPorte HM, Gao X, Eby JM, Cheng YH, Nevins AM, Volkman BF, Gaponenko V, Majetschak M. Identification and functional characterization of arginine vasopressin receptor 1A – atypical chemokine receptor 3 heteromers in vascular smooth muscle. Open Biol. 2018 Jan;8(1). pii: 170207.

Albee LJ, Eby JM, Tripathi A, LaPorte HM, Gao X, Volkman BF, Gaponenko V, Majetschak M. α1-Adrenergic receptors function within hetero-oligomeric complexes with atypical chemokine receptor 3 and chemokine (C-X-C motif) receptor 4 in vascular smooth muscle cells. J Am Heart Assoc. 2017 Aug 17;6(8). pii: e006575. doi: 10.1161/JAHA.117.006575.

Evans AE, Tripathi A, LaPorte HM, Brueggemann LI, Abhay Kumar Singh, Albee LJ, Byron KL, Tarasova NI, Volkman BF, Thomas Yoonsang Cho, Gaponenko V, Majetschak M. New insights into mechanisms and functions of chemokine (C-X-C motif) receptor 4 heteromerization in vascular smooth muscle. Int J Mol Sci, 2016 Jun 20;17(5): E971.

Tripathi A, Vana PG, Chavan TS, Brueggemann LI, Byron KL, Tarasova NI, Volkman BF, Gaponenko V, Majetschak M. Heteromerization of chemokine (C-X-C motif) receptor 4 with α1A/B-adrenergic receptors controls α1-adrenergic receptor function. Proc Natl Acad Sci U S A, 2015;112(13):E1659-68.