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Alternative splicing of human metabotropic glutamate receptor 3
Author(s) -
Sartorius Leah J.,
Nagappan Guhan,
Lipska Barbara K.,
Lu Bai,
Sei Yoshitatsu,
RenPatterson Renee,
Li Zhen,
Weinberger Daniel R.,
Harrison Paul J.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03609.x
Subject(s) - biology , alternative splicing , metabotropic glutamate receptor 3 , rna splicing , exon , metabotropic glutamate receptor , transmembrane domain , glutamate receptor , genetics , amino acid , receptor , gene , rna
The metabotropic glutamate receptor 3 (GRM3, mGluR3) is important in regulating synaptic glutamate. Here, we report the existence of three splice variants of GRM3 in human brain arising from exon skipping events. The transcripts are expressed in prefrontal cortex, hippocampus and cerebellum, and in B lymphoblasts. We found no evidence for alternative splicing of GRM2. The most abundant GRM3 variant lacks exon 4 (GRM3Δ4). In silico translation analysis of GRM3Δ4 predicts a truncated protein with a conserved extracellular ligand binding domain, absence of a seven‐transmembrane domain, and a unique 96‐amino acid C‐terminus. When expressed in rat hippocampal neurons, GRM3Δ4 is translated into a 60 kDa protein. Immunostaining and cell fractionation data indicate that the truncated protein is primarily membrane‐associated. An antibody developed against the GRM3Δ4 C‐terminus detects a protein of approximately 60 kDa in human brain lysates and in B lymphoblasts, suggesting translation of GRM3Δ4 in vivo . The existence of the GRM3Δ4 isoform is relevant in the light of the reported association of non‐coding single nucleotide polymorphisms (SNPs) in GRM3 with schizophrenia, and with the potential of GRM3 as a therapeutic target for several neuropsychiatric disorders.