GABAB Receptor Association with the PDZ Scaffold Mupp1 Alters Receptor Stability and Function

γ-Aminobutyric acid, type B (GABAB) receptors are heterodimeric G protein-coupled receptors that mediate slow inhibitory synaptic transmission in the central nervous system. To identify novel interacting partners that might regulate GABAB receptor (GABABR) functionality, we screened the GABABR2 carb...

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Bibliographic Details
Published in:The Journal of biological chemistry 2007-02, Vol.282 (6), p.4162-4171
Main Authors: Balasubramanian, Srividya, Fam, Sami R., Hall, Randy A.
Format: Article
Language:English
Subjects:
Adaptor Proteins, Signal Transducing - metabolism
Adaptor Proteins, Signal Transducing - physiology
Animals
Carrier Proteins - metabolism
Carrier Proteins - physiology
Cell Adhesion Molecules
Cell Line
Cells, Cultured
Chlorocebus aethiops
COS Cells
Humans
Intracellular Signaling Peptides and Proteins
Membrane Proteins
Neoplasm Proteins - metabolism
Neoplasm Proteins - physiology
Protein Binding
Proteome - chemistry
Proteome - metabolism
Rats
Rats, Sprague-Dawley
Receptors, GABA-B - genetics
Receptors, GABA-B - metabolism
Receptors, GABA-B - physiology
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Summary:γ-Aminobutyric acid, type B (GABAB) receptors are heterodimeric G protein-coupled receptors that mediate slow inhibitory synaptic transmission in the central nervous system. To identify novel interacting partners that might regulate GABAB receptor (GABABR) functionality, we screened the GABABR2 carboxyl terminus against a recently created proteomic array of 96 distinct PDZ (PSD-95/Dlg/ZO-1 homology) domains. The screen identified three specific PDZ domains that exhibit interactions with GABABR2: Mupp1 PDZ13, PAPIN PDZ1, and Erbin PDZ. Biochemical analysis confirmed that full-length Mupp1 and PAPIN interact with GABABR2 in cells. Disruption of the GABABR2 interaction with PDZ scaffolds by a point mutation to the carboxyl terminus of the receptor dramatically decreased receptor stability and attenuated the duration of GABAB receptor signaling. The effects of mutating the GABABR2 carboxyl terminus on receptor stability and signaling were mimicked by small interference RNA knockdown of endogenous Mupp1. These findings reveal that GABAB receptor stability and signaling can be modulated via GABABR2 interactions with the PDZ scaffold protein Mupp1, which may contribute to cell-specific regulation of GABAB receptors in the central nervous system.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M607695200