Biomaterial Database

The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. 2010

Claire E Bamberg, and Charles R Mackay, and Hyun Lee, and David Zahra, and Jenny Jackson, and Yun Si Lim, and Peter L Whitfeld, and Stewart Craig, and Erin Corsini, and Bao Lu, and Craig Gerard, and Norma P Gerard

Pulmonary Division, Department of Pediatrics, Children's Hospital, Boston, Massachusetts 02115, USA.

The complement anaphylatoxin C5a is a proinflammatory component of host defense that functions through two identified receptors, C5a receptor (C5aR) and C5L2. C5aR is a classical G protein-coupled receptor, whereas C5L2 is structurally homologous but deficient in G protein coupling. In human neutrophils, we show C5L2 is predominantly intracellular, whereas C5aR is expressed on the plasma membrane. Confocal analysis shows internalized C5aR following ligand binding is co-localized with both C5L2 and beta-arrestin. Antibody blockade of C5L2 results in a dramatic increase in C5a-mediated chemotaxis and ERK1/2 phosphorylation but does not alter C5a-mediated calcium mobilization, supporting its role in modulation of the beta-arrestin pathway. Association of C5L2 with beta-arrestin is confirmed by cellular co-immunoprecipitation assays. C5L2 blockade also has no effect on ligand uptake or C5aR endocytosis in human polymorphonuclear leukocytes, distinguishing its role from that of a rapid recycling or scavenging receptor in this cell type. This is thus the first example of a naturally occurring seven-transmembrane segment receptor that is both obligately uncoupled from G proteins and a negative modulator of signal transduction through the beta-arrestin pathway. Physiologically, these properties provide the possibility for additional fine-tuning of host defense.

UI	MeSH Term	Description	Entries
D008810	Mice, Inbred C57BL	One of the first INBRED MOUSE STRAINS to be sequenced. This strain is commonly used as genetic background for transgenic mouse models. Refractory to many tumors, this strain is also preferred model for studying role of genetic variations in development of diseases.	Mice, C57BL,Mouse, C57BL,Mouse, Inbred C57BL,C57BL Mice,C57BL Mice, Inbred,C57BL Mouse,C57BL Mouse, Inbred,Inbred C57BL Mice,Inbred C57BL Mouse
D008958	Models, Molecular	Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.	Molecular Models,Model, Molecular,Molecular Model
D009504	Neutrophils	Granular leukocytes having a nucleus with three to five lobes connected by slender threads of chromatin, and cytoplasm containing fine inconspicuous granules and stainable by neutral dyes.	LE Cells,Leukocytes, Polymorphonuclear,Polymorphonuclear Leukocytes,Polymorphonuclear Neutrophils,Neutrophil Band Cells,Band Cell, Neutrophil,Cell, LE,LE Cell,Leukocyte, Polymorphonuclear,Neutrophil,Neutrophil Band Cell,Neutrophil, Polymorphonuclear,Polymorphonuclear Leukocyte,Polymorphonuclear Neutrophil
D002460	Cell Line	Established cell cultures that have the potential to propagate indefinitely.	Cell Lines,Line, Cell,Lines, Cell
D002634	Chemotaxis, Leukocyte	The movement of leukocytes in response to a chemical concentration gradient or to products formed in an immunologic reaction.	Leukotaxis,Leukocyte Chemotaxis
D004789	Enzyme Activation	Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.	Activation, Enzyme,Activations, Enzyme,Enzyme Activations
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000071557	beta-Arrestins	Non-visual system arrestins that negatively regulate G-PROTEIN-COUPLED RECEPTORS (GPCRs) and may also function independently of GPCR signaling. They bind and recruit many different signaling factors, including MITOGEN-ACTIVATED PROTEIN KINASES; SRC-FAMILY-KINASES; and FILAMIN to GPCRs and may recognize different phosphorylation states of the receptors to determine the specificity of the cellular response to signaling.	beta-Arrestin,beta Arrestin,beta Arrestins
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D014018	Tissue Distribution	Accumulation of a drug or chemical substance in various organs (including those not relevant to its pharmacologic or therapeutic action). This distribution depends on the blood flow or perfusion rate of the organ, the ability of the drug to penetrate organ membranes, tissue specificity, protein binding. The distribution is usually expressed as tissue to plasma ratios.	Distribution, Tissue,Distributions, Tissue,Tissue Distributions