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GABA-A receptor trafficking and domain interaction with GABA-A receptor associated protein



GABA-A receptor trafficking and domain interaction with GABA-A receptor associated protein



Society for Neuroscience Abstracts 27(1): 84



We showed previously that GABARAP is associated with and promotes the clustering of GABA-A receptors (GABAR), and modulate the channel kinetics (PNAS 97, 11557-11562). In this study, using GFP-tagged alpha 1 or gamma2 subunit, we are able to monitor the trafficking of GABAR and observe the pattern of distribution in living QT-6 cells. After transfecting the cell with plasmids encoding alpha1, beta2, gamma2 subunits and GABARAP, GABAR first appeared in the peri-nuclear area, then diffusely in the Whole cytoplasm. Clusters of the receptor can be seen in cytoplasm and on plasma membrane at 24 hr, but only in 10% of the cells. After 48 hr expression, 40-50% of cells showed clusters, and at 72 hr, more than 70% of the cells have clusters both in cytoplasm and on the membrane. The domain interactions between GABAR and GABARAP were studied with the yeast two-hybrid screen, in vitro binding and QT-6 cell clustering assay. The yeast two-hybrid screen identified GABARAP (36-117) and gamma2(394-411) as the binding domains. In vitro binding experiments indicate that the binding of GABARAP to GABAR was inhibited by GABARAP (36-117) and gamma2(394-411). QT-6 cell clustering assay showed that Antennapedia-gamma2(394-411) inhibits GABAR clustering in a time- and dose-dependent manner.

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