Phospholipase C-related Inactive Protein is Involved in Trafficking of Gamma2 Subunit-containing Gaba(A) Receptors to the Cell Surface.
From: Laboratory of Molecular and Cellular Biochemistry, Faculty of Dental Science, and Station for Collaborative Research, Kyushu University, Fukuoka 812-8582, Japan.
The Journal of neuroscience : the official journal of the Society for Neuroscience
- Publish Date: Feb 2007
- ISSN: 1529-2401
- Volume: 27
- Issue: 7
- Pages: 1692-701
- Medium: Internet
- Language: English
- Citation (JAMA): Mizokami Akiko, Kanematsu Takashi, Ishibashi Hitoshi, et al. Phospholipase C-related Inactive Protein is Involved in Trafficking of Gamma2 Subunit-containing Gaba(A) Receptors to the Cell Surface.. J. Neurosci. Feb 2007;27:1692-701
Abstract
The subunit composition of GABA(A) receptors is known to be associated with distinct physiological and pharmacological properties. Previous studies that used phospholipase C-related inactive protein type 1 knock-out (PRIP-1 KO) mice revealed that PRIP-1 is involved in the assembly and/or the trafficking of gamma2 subunit-containing GABA(A) receptors. There are two PRIP genes in mammals; thus the roles of PRIP-1 might be compensated partly by those of PRIP-2 in PRIP-1 KO mice. Here we used PRIP-1 and PRIP-2 double knock-out (PRIP-DKO) mice and examined the roles for PRIP in regulating the trafficking of GABA(A) receptors. Consistent with previous results, sensitivity to diazepam was reduced in electrophysiological and behavioral analyses of PRIP-DKO mice, suggesting an alteration of gamma2 subunit-containing GABA(A) receptors. The surface numbers of diazepam binding sites (alpha/gamma2 subunits) assessed by [3H]flumazenil binding were reduced in the PRIP-DKO mice as compared with those of wild-type mice, whereas the cell surface GABA binding sites (alpha/beta subunits, assessed by [3H]muscimol binding) were increased in PRIP-DKO mice. The association between GABA(A) receptors and GABA(A) receptor-associated protein (GABARAP) was reduced significantly in PRIP-DKO neurons. Disruption of the direct interaction between PRIP and GABA(A) receptor beta subunits via the use of a peptide corresponding to the PRIP-1 binding site reduced the cell surface expression of gamma2 subunit-containing GABA(A) receptors in cultured cell lines and neurons. These results suggest that PRIP is implicated in the trafficking of gamma2 subunit-containing GABA(A) receptors to the cell surface, probably by acting as a bridging molecule between GABARAP and the receptors.
Mesh Headings (Keywords): Animals, Animals, Newborn, Behavior, Animal, Carrier Proteins, Cells, Cultured, Dose-Response Relationship, Drug, Enzyme-Linked Immunosorbent Assay, GABA Agents, Hippocampus, Humans, Immunoprecipitation, Male, Membrane Potentials, Mice, Mice, Inbred C57BL, Mice, Knockout, Neurons, Patch-Clamp Techniques, Protein Binding, Protein Subunits, Protein Transport, RNA, Messenger, Receptors, GABA-A, Reverse Transcriptase Polymerase Chain Reaction, Transfection
Check for Full Text / PubMed Unique Identifier (PMID): 17301177
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