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- Title
Phospholipase C-related inactive protein is implicated in the constitutive internalization of GABA<sub>A</sub> receptors mediated by clathrin and AP2 adaptor complex.
- Authors
Kanematsu, Takashi; Fujii, Makoto; Mizokami, Akiko; Kittler, Josef T.; Nabekura, Junichi; Moss, Stephen J.; Hirata, Masato
- Abstract
A mechanism for regulating the strength of synaptic inhibition is enabled by altering the number of GABAA receptors available at the cell surface. Clathrin and adaptor protein 2 (AP2) complex-mediated endocytosis is known to play a fundamental role in regulating cell surface GABAA receptor numbers. Very recently, we have elucidated that phospholipase C-related catalytically inactive protein (PRIP) molecules are involved in the phosphorylation-dependent regulation of the internalization of GABAA receptors through association with receptor β subunits and protein phosphatases. In this study, we examined the implications of PRIP molecules in clathrin-mediated constitutive GABAA receptor endocytosis, independent of phospho-regulation. We performed a constitutive receptor internalization assay using human embryonic kidney 293 (HEK293) cells transiently expressed with GABAA receptor α/β/γ subunits and PRIP. PRIP was internalized together with GABAA receptors, and the process was inhibited by PRIP-binding peptide which blocks PRIP binding to β subunits. The clathrin heavy chain, μ2 and β2 subunits of AP2 and PRIP-1, were complexed with GABAA receptor in brain extract as analyzed by co-immunoprecipitation assay using anti-PRIP-1 and anti-β2/3 GABAA receptor antibody or by pull-down assay using β subunits of GABAA receptor. These results indicate that PRIP is primarily implicated in the constitutive internalization of GABAA receptor that requires clathrin and AP2 protein complex.
- Subjects
GABA receptors; CELL membranes; PROTEINS; ENDOCYTOSIS; PHOSPHOLIPASE C
- Publication
Journal of Neurochemistry, 2007, Vol 101, Issue 4, p898
- ISSN
0022-3042
- Publication type
Article
- DOI
10.1111/j.1471-4159.2006.04399.x