Down-Regulation of GABAA Receptor via Promiscuity with the Vasoactive Peptide Urotensin II Receptor. Potential Involvement in Astrocyte Plasticity
Figure 12
Schematic model depicting the mechanism of UT-mediated GABAAR down-regulation.
UII efficiently activates the G protein-coupled receptor UT, leading to a fast short-term decrease of the chloride current not sustained by G proteins, calcium, phosphorylation and endocytosis processes. This rapid effect involves the distal 19 C-terminal amino acids of UT and the presence of γ subunits within of the GABAAR complex (1). During the washout period, a long-term inhibition develops via a dynamin-, calcium- and phosphorylation-dependent endocytic mechanisms, requiring at least in part the 351–370 sequence of UT and GABAAR γ subunits (2). It is hypothesized that the directional cross-talk between UT and GABAAR, and the extinction of the latter at the plasma membrane, may relay transition from quiescent to proliferant astrocytes.