Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 7633 - 7644 |
| Number of pages | 12 |
| Journal | Journal of Biological Chemistry |
| Volume | 285 |
| Issue number | 10 |
| DOIs | |
| Publication status | Published - 2010 |
| Externally published | Yes |
Cite this
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The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction. / Bamberg, Claire E; Mackay, Charles; Lee, Hyun; Zahra, David; Jackson, Jenny; Lim, Yun Si; Whitfeld, Peter L; Craig, Stewart; Corsini, Erin; Lu, Bao; Gerard, Craig; Gerard, Norman P.
In: Journal of Biological Chemistry, Vol. 285, No. 10, 2010, p. 7633 - 7644.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - The C5a receptor (C5aR) C5L2 is a modulator of C5aR-mediated signal transduction
AU - Bamberg, Claire E
AU - Mackay, Charles
AU - Lee, Hyun
AU - Zahra, David
AU - Jackson, Jenny
AU - Lim, Yun Si
AU - Whitfeld, Peter L
AU - Craig, Stewart
AU - Corsini, Erin
AU - Lu, Bao
AU - Gerard, Craig
AU - Gerard, Norman P
PY - 2010
Y1 - 2010
N2 - 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 I?-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.
AB - 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 I?-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.
UR - http://www.jbc.org/content/285/10/7633.full.pdf+html
U2 - 10.1074/jbc.M109.092106
DO - 10.1074/jbc.M109.092106
M3 - Article
VL - 285
SP - 7633
EP - 7644
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
SN - 1083-351X
IS - 10
ER -