Alternative splicing of human metabotropic glutamate receptor 3

Department of Psychiatry, University of Oxford, Warneford Hospital, Oxford, UK.
Journal of Neurochemistry (Impact Factor: 4.24). 03/2006; 96(4):1139-48. DOI: 10.1111/j.1471-4159.2005.03609.x
Source: PubMed

ABSTRACT 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 (GRM3Delta4). In silico translation analysis of GRM3Delta4 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, GRM3Delta4 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 GRM3Delta4 C-terminus detects a protein of approximately 60 kDa in human brain lysates and in B lymphoblasts, suggesting translation of GRM3Delta4 in vivo. The existence of the GRM3Delta4 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.

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Available from: Barbara K Lipska, Oct 17, 2014
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    • "Other isoforms such as mGlu5c, 5d and 5e have been reported in humans (Minakami et al., 1994). Exon-skipping events lead to three spliced variants in mGlu3 (Sartorius et al., 2006). For group III receptors, mGlu4 exists as mGlu4a, and mGlu4b (Thomsen et al., 1997). "
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    • "Three splice variants of GRM3 have been reported in human brain and B lymphoblasts. The most abundant variant lacks exon 4 (GRM3D4) and encodes for a 60 kDa protein lacking the 7-TM domain of mGlu3 receptors (Sartorius et al., 2006). "
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    • "The mGluR2 and mGluR3 probes were designed to detect full length transcripts of each gene. The mGluR3 probe detects full length mGluR3 as well as the alternate transcript missing exon 4 (Sartorius et al, 2006). "
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