Function: Okamoto et al. (1998) expressed mGlur1-alpha (mGluR1A) in insect cells on a baculovirus system. They isolated a soluble mGluR that encodes only the extracellular domain and retains a ligand binding characteristic similar to that of the full-length receptor. Their observations demonstrated that a ligand binding event in mGluRs can be dissociated from the membrane domain.

Function: Smitt et al. (2000) demonstrated that autoantibody against mGluR1A was responsible for severe paraneoplastic cerebellar ataxia in 2 patients. The disorder developed in both patients while they were in remission from Hodgkin disease (OMIM:236000). One, a teenager, had been in remission for 2 years when truncal ataxia, intention tremor, and gait ataxia developed. This patient improved clinically with loss of cells in the cerebrospinal fluid when treated with plasma exchanges, oral prednisone, and 2 courses of intravenous immune globulin. The second patient reported by Smitt et al. (2000) was in her late forties and, in addition to successfully treated Hodgkin disease, had polycystic kidney disease requiring hemodialysis for many years. Therapy was less successful in this patient, possibly because of delay in initiation.

Function: G protein-coupled receptors (GPCRs) transduce signals from extracellular transmitters to the inside of the cell by activating G proteins. Mutation and overexpression of these receptors have revealed that they can reach their active state even in the absence of agonist, as a result of a natural shift in the equilibrium between their inactive and active conformations. Such agonist-independent (constitutive) activity has been observed for the glutamate GPCRs (the metabotropic glutamate receptors mGluR1a and mGluR5) when they are overexpressed in heterologous cells. Ango et al. (2001) demonstrated that in neurons, the constitutive activity of these receptors is controlled by Homer proteins (e.g., OMIM:604798), which bind directly to the receptors' carboxy-terminal intracellular domains. Disruption of this interaction by mutagenesis or antisense strategies, or expression of endogenous Homer1a, induces constitutive activity in mGluR1a or mGluR5. Ango et al. (2001) concluded that these glutamate GPCRs can be directly activated by intracellular proteins as well as by agonists.

Function: One prominent action of group I mGluRs is to protect neurons from apoptotic death (Copani et al., 1995; Maiese et al., 2000). Using immunoprecipitation studies in rat, Rong et al. (2003) found that the PI3 kinase enhancer PIKE-L (OMIM:605476) binds to Homer-1C, an adaptor protein that is localized to postsynaptic densities. Activation of mGluR5 enhanced formation of an mGluRI-Homer-PIKE-L complex, leading to activation of PI3K activity and prevention of apoptosis in cultured neurons.

Function: Kim et al. (2003) reported that the mGluR1-evoked slow excitatory postsynaptic conductance (EPSC) is mediated by the TRPC1 (OMIM:602343) cation channel. TRPC1 is expressed in perisynaptic regions of the cerebellar parallel fiber-Purkinje cell synapse and is physically associated with mGluR1. Manipulations that interfere with TRPC1 block the mGluR1-evoked slow EPSC in Purkinje cells; however, fast transmission mediated by AMPA-type glutamate receptors remains unaffected. Kim et al. (2003) further demonstrated that coexpression of mGluR1 and TRPC1 in a heterologous system reconstituted an mGluR1-evoked conductance that closely resembles the slow EPSC in Purkinje cells.

Summary

Top-ranked sequences

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            ||||||||||||||||||||||||||||||#||||||||||||||||||||||||||||||
Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            |||| |||||||||||||||||||||||||#|||||||||||||||||||||||||||||+
Sbjct   907 QHMWQRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPV  966

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            |||| |||||||||||||||||||||||||#|||||||||||||||||||||||||||||+
Sbjct    20 QHMWQRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPV   79

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            ||||||||||||||||||||||||||||||#||||||||||||||||||||| |||||||+
Sbjct   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNV-EEEDAQPV  965

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            |||||||||||| |||||||||||||||||#||||||||||||||||||||| |||||||+
Sbjct   907 QHMWHRLSVHVKANETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNV-EEEDAQPV  965

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQP  965
            ||||||||||||+||| |||||||||||||#|||||||||||| |||||||| |||+++|
Sbjct   907 QHMWHRLSVHVKSNETPCNQTAVIKPLTKS#YQGSGKSLTFSDNSTKTLYNVVEEEESEP  965

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEED  962
            ||+| |||||||||||||||||||||||||#|||||||||||| |||||||||||++
Sbjct   907 QHVWQRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDASTKTLYNVEEEDN  962

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEED  962
            ||+| |||||||||||||||||||||||||#|||||||||||| |||||||||||++
Sbjct   907 QHVWQRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDASTKTLYNVEEEDN  962

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            +|||||||||||  || |||||||||||||#| |  |||||+| |+||||||||||| +|+
Sbjct   899 EHMWHRLSVHVKNQETGCNQTAVIKPLTKS#YHGQSKSLTFTDISSKTLYNVEEEEDREPV  958

Query   907 QHMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQPI  966
            +|||||||||||  |   ||||+||||| +#|   |  + ||| |||||||| ||++  ||
Sbjct   907 EHMWHRLSVHVKKQEAGSNQTAIIKPLTNT#YNNPG--MEFSDLSTKTLYNVAEEDEIDPI  964

Query   908 HMWHRLSVHVKTNETACNQTAVIKPLTKS#YQGSGKSLTFSDTSTKTLYNVEEEEDAQ  964
            |||||||||||  |+  || ||||||| +#||     | ||+ |||||||| ||++++
Sbjct   978 HMWHRLSVHVKRQESGSNQMAVIKPLTNT#YQ---NRLEFSNLSTKTLYNVAEEDESE 1031

Query   907 QHMWHRLSVHVKTNETAC-NQTAVIKPLTKS#YQGSGKSLT--FSDTSTKTLYNVEEEEDA  963
            +| | |||||||  |  | || |||+||| +#|  +| |+   ||| |||||||| ||+++
Sbjct   915 EHNWQRLSVHVKRQEAGCSNQMAVIRPLTNT#YHNTGSSMAMEFSDLSTKTLYNVAEEDES  974

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[PubMed ID: 9069287] ... Brakeman PR, Lanahan AA, O'Brien R, Roche K, Barnes CA, Huganir RL, Worley PF, Homer: a protein that selectively binds metabotropic glutamate receptors. Nature. 1997 Mar 20;386(6622):284-8.

[PubMed ID: 9076744] ... Stephan D, Bon C, Holzwarth JA, Galvan M, Pruss RM, Human metabotropic glutamate receptor 1: mRNA distribution, chromosome localization and functional expression of two splice variants. Neuropharmacology. 1996;35(12):1649-60.

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