T Cell Chemotaxis to Lysophosphatidylcholine through the G2A Receptor

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 101; no. 1; pp. 245 - 250
• Main Authors: Radu, Caius G., Yang, Li V., Riedinger, Mireille, Au, Matthew, Witte, Owen N.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 06.01.2004; National Acad Sciences
• Subjects: Anatomy & physiology; Animals; Antibodies; Autoimmunity; Base Sequence; Biological Sciences; Cell Cycle Proteins - genetics; Cell Cycle Proteins - immunology; Cell Line; Cell lines; Cells; Chemotaxis; Chemotaxis, Leukocyte - immunology; Genetics; HeLa cells; Immunology; Lipids; Lymphocytes; Lysophosphatidylcholines - immunology; Mice; Mice, Knockout; Molecules; Proteins; Receptors; Receptors, G-Protein-Coupled - deficiency; Receptors, G-Protein-Coupled - genetics; Receptors, G-Protein-Coupled - immunology; Ribonucleic acid; RNA; RNA Interference; RNA, Small Interfering - genetics; Rodents; Small interfering RNA; Stromal cells; Studies; T lymphocytes; T-Lymphocytes - immunology
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.2536801100

G2A is an immunoregulatory G protein-coupled receptor predominantly expressed in lymphocytes and macrophages. Ectopic overexpression studies have implicated G2A as a receptor for the bioactive lysophospholipid, lysophosphatidylcholine (LPC). However, the functional consequences of LPC-G2A interaction at physiological levels of receptor expression, and in a cellular context relevant to its immunological role, remain largely unknown. Here, we show impaired chemotaxis to LPC of a T lymphoid cell line in which G2A expression was chronically down-regulated by RNA interference technology. Rescuing this phenotype by reconstitution of the physiological level of receptor expression further supports a functional connection between LPC-G2A interaction and cellular motility. Overexpression of G2A in the T lymphoid cell line significantly enhanced chemotaxis to LPC. It also modified migration toward the LPC-related molecule, lysophosphatidic acid, indicating the possibility of crosstalk between G2A and endogenous lysophosphatidic acid receptors. The role of G2A in LPC-mediated cell migration may be relevant to the autoimmune syndrome associated with genetic inactivation of this G protein-coupled receptor in mice. The experimental system described here can be useful for understanding the structural requirements for LPC recognition by G2A and the signaling pathways regulated by this ligand-receptor pair.