title: T cell chemotaxis to lysophosphatidylcholine through the G2A receptor.
abstract: 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.
authors.affiliation: Department of Microbiology, Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095, USA.
authors.forename: Caius G
authors.initials: CG
authors.lastname: Radu
authors.forename: Li V
authors.initials: LV
authors.lastname: Yang
authors.forename: Mireille
authors.initials: M
authors.lastname: Riedinger
authors.forename: Matthew
authors.initials: M
authors.lastname: Au
authors.forename: Owen N
authors.initials: ON
authors.lastname: Witte
mesh_terms: D000818:Animals; D015551:Autoimmunity; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000276:immunology*; D008244:Lysophosphatidylcholines / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000172:deficiency / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D018797:Cell Cycle Proteins; C115270:G2A receptor; D008244:Lysophosphatidylcholines; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled