Characterization of mGluR5R, a novel, metabotropic glutamate receptor 5-related gene.
We report here the isolation of a novel gene termed mGluR5R (mGluR5-related). The N-terminus of mGluR5R is highly similar to the extracellular domain of metabotropic glutamate receptor 5 (mGluR5) whereas the C-terminus bears similarity to the testis-specific gene, RNF18. mGluR5R is expressed in the human CNS in a coordinate fashion with mGluR5. Although the sequence suggests that mGluR5R may be a secreted glutamate binding protein, we found that when expressed in HEK293 cells it was membrane associated and not secreted. Furthermore, mGluR5R was incapable of binding the metabotropic glutamate receptor class I selective agonist, quisqualate. Although mGluR5R could not form disulfide-mediated covalent homodimers, it was able to form a homomeric complex, presumably through noncovalent interactions. mGluR5R also formed noncovalent heteromeric associations with an engineered construct of the extracellular domain of mGluR5 as well as with full-length mGluR5 and mGluR1alpha. The ability of mGluR5R to associate with mGluR1alpha and mGluR5 suggests that it may be a modulator of class I metabotropic glutamate receptor function.
Bates
Brian
B
Wyeth Research, Functional Genomics, 35 Cambridge Park Drive, Cambridge, MA 02140, USA. bbates@wyeth.com
Xie
Yuhong
Y
Taylor
Noel
N
Johnson
Jeremy
J
Wu
Leeying
L
Kwak
Seung
S
Blatcher
Maria
M
Gulukota
Kamalakar
K
Paulsen
Janet E
JE
D000595:Amino Acid Sequence; D002352:Carrier Proteins / Q000235:genetics; D002458:Cell Fractionation; D002460:Cell Line; D002490:Central Nervous System / Q000378:metabolism; D017077:Culture Media, Conditioned; D018690:Excitatory Amino Acid Agonists / Q000378:metabolism; D006801:Humans; D046911:Macromolecular Substances; D008969:Molecular Sequence Data; D011485:Protein Binding; D016318:Quisqualic Acid / Q000378:metabolism; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics* / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D016415:Sequence Alignment
D002352:Carrier Proteins; D017077:Culture Media, Conditioned; D018690:Excitatory Amino Acid Agonists; C578935:GRM5 protein, human; D046911:Macromolecular Substances; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D011993:Recombinant Fusion Proteins; C416947:TRIM49 protein, human; D016318:Quisqualic Acid