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Complement component 5a receptor oligomerization and homologous receptor down-regulation
- Source :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (45), pp.31038-46. ⟨10.1074/jbc.M805260200⟩, Journal of Biological Chemistry, 2008, 283 (45), pp.31038-46. ⟨10.1074/jbc.M805260200⟩
- Publication Year :
- 2008
- Publisher :
- HAL CCSD, 2008.
-
Abstract
- National audience; Most G-protein-coupled receptors (GPCRs) form di(oligo)-meric structures that constitute signaling and trafficking units and might be essential for receptor functions. Cell responses to complement C5a receptor (C5aR) are tightly controlled by receptor desensitization and internalization. To examine the implication of dimerization in C5aR regulation, we generated an NH(2)-terminally modified C5aR mutant, unable to bind C5a, and a phosphorylation-deficient mutant. Neither an intact NH(2) terminus nor the presence of COOH-terminal phosphorylation sites appeared to be required for the formation of C5aR dimers. Upon C5a stimulation, mutant receptors did not internalize when individually expressed. C5a stimulation of cells that co-expressed wild type C5aR together with either unliganded or phosphorylation-deficient mutant resulted in co-internalization of mutant receptors with C5aR. Unliganded GPCRs can be cross-phosphorylated within a heterologous receptor dimer or by second messenger-activated kinases. C5a stimulation of (32)P-labeled cells that co-expressed the unliganded mutant with either C5aR or the phosphorylation-deficient mutant did not induce phosphorylation of the unliganded mutant. We can thus postulate that, in the case of C5aR, the stimulation and phosphorylation of one monomer is enough to lead to dimer internalization. The existence and functional implication of di(oligo)mer formation may be important for an accurate C5aR down-regulation in pathological conditions.
- Subjects :
- MESH: Mutation
media_common.quotation_subject
Mutant
Down-Regulation
Stimulation
Complement C5a
MESH: Receptors, G-Protein-Coupled
Biology
Biochemistry
MESH: Down-Regulation
Cell Line
Receptors, G-Protein-Coupled
03 medical and health sciences
MESH: Receptor Aggregation
0302 clinical medicine
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology
Phosphorylation
Internalization
Receptor
Molecular Biology
Receptor, Anaphylatoxin C5a
030304 developmental biology
media_common
G protein-coupled receptor
Receptor Aggregation
0303 health sciences
MESH: Humans
MESH: Phosphorylation
Protein Synthesis, Post-Translational Modification, and Degradation
Wild type
Cell Biology
Cell biology
Receptors, Complement
MESH: Cell Line
MESH: Receptors, Complement
MESH: Dimerization
Mutation
MESH: Complement C5a
Dimerization
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 00219258 and 1083351X
- Database :
- OpenAIRE
- Journal :
- Journal of Biological Chemistry, Journal of Biological Chemistry, American Society for Biochemistry and Molecular Biology, 2008, 283 (45), pp.31038-46. ⟨10.1074/jbc.M805260200⟩, Journal of Biological Chemistry, 2008, 283 (45), pp.31038-46. ⟨10.1074/jbc.M805260200⟩
- Accession number :
- edsair.doi.dedup.....41955e50972e42f996deeafea478ecb0