Functional studies on CXCR4 heterodimerization

Abstract

G-protein coupled receptors (GPCRs) transit extracellular ques to a series of internal signals. Many GPCRs with different function are in charge of diverse signaling pathways. C-X-C chemokine receptor type 4 (CXCR4) is involved in a class of GPCRs which mediates cell migration and development of immune cells. In tumor cells, extensive studies have identified its distinct roles in development and metastasis. There have been constraints on clinical researches with this indispensable CXCR4, because direct down-regulation of it was catastrophic to cell viability. To deal with CXCR4, cancer cell-specific regulation of CXCR4, not globally affecting normal tissue, is required. Recent findings elucidated that GPCRs are more often found as functional dimers or oligomers rather than monomers. In this study, BiFC and co-internalization analysis were utilized to sort out GPCRs interacting with CXCR4. Indirect regulation of cyclic AMP and calcium signaling by CXCR4 dimerization demonstrated in this study suggests new possibilities and directions of CXCR4-target drug research.