Identification of functional domains in the formyl peptide receptor-like 1 for agonist-induced cell chemotaxis.
Formyl peptide receptor-like 1 (FPRL1) is a seven transmembrane domain, G protein-coupled receptor that interacts with a variety of exogenous and host-derived agonists. In order to identify domains crucial for ligand recognition by FPRL1, we used chimeric receptors with segments in FPRL1 replaced by corresponding amino acid sequences derived from the prototype formyl peptide receptor FPR. The chimeric receptors were stably transfected into human embryonic kidney epithelial cells and the capacity of the cells to migrate in response to formyl peptide receptor agonists was evaluated. Our results showed that multiple domains in FPRL1 are involved in the receptor response to chemotactic agonists with the sixth transmembrane domain and the third extracellular loop playing a prominent role. Interestingly, the N-terminus and a segment between the fourth transmembrane domain and the third intracellular loop of FPRL1 are important for receptor interaction with a 42 amino acid amyloid beta peptide (Abeta42), an Alzheimer's disease-associated FPRL1 agonist, but not with MMK-1, a synthetic FPRL1 agonist, suggesting that diverse agonists may use different domains in FPRL1. Considering the potential importance of FPRL1 in inflammation and neurodegenerative diseases, the identification of functional domains in this receptor will provide valuable information for the design of specific receptor antagonists.
Le
Yingying
Y
Laboratory of Molecular Immunoregulation, Center for Cancer Research, National Cancer Institute at Frederick, MD, USA.
Ye
Richard D
RD
Gong
Wanghua
W
Li
Jianxiang
J
Iribarren
Pablo
P
Wang
Ji Ming
JM
D000595:Amino Acid Sequence; D002460:Cell Line; D002633:Chemotaxis; D006801:Humans; D008969:Molecular Sequence Data; D044042:Receptors, Formyl Peptide / Q000819:agonists / Q000737:chemistry* / Q000502:physiology
C469986:FPR1 protein, human; D044042:Receptors, Formyl Peptide