GABAAReceptor Phospho-Dependent Modulation Is Regulated by Phospholipase C-Related Inactive Protein Type 1, a Novel Protein Phosphatase 1 Anchoring Protein

• DOI: 10.1523/jneurosci.1323-04.2004
• Publication Date: 2004-08-11T18:27:34Z
• Authors: Miho Terunuma; Il-Sung Jang; Sang Hoon Ha; Josef T. Kittler; Takashi Kanematsu; Jasmina N. Jovanovic; Keiichi I. Nakayama; Norio Akaike; Sung Ho Ryu; Stephen J. Moss; Masato Hirata
• Keywords: STRUCTURAL BASIS; 0301 basic medicine; Patch-Clamp Techniques; receptor; KINASE-C; Receptors, Cytoplasmic and Nuclear; In Vitro Techniques; RAT-BRAIN; Hippocampus; phosphatase; GABA; Mice; 03 medical and health sciences; cAMP; Protein Phosphatase 1; Phosphoprotein Phosphatases; Animals; Inositol 1,4,5-Trisphosphate Receptors; CELL-SURFACE EXPRESSION; CATALYTIC SUBUNIT; Phosphorylation; 130 KDA PROTEIN; Mice, Knockout; phosphorylation; Receptors, Dopamine D1; protein kinase; PYRAMIDAL NEURONS; Receptors, GABA-A; Cyclic AMP-Dependent Protein Kinases; A RECEPTORS; Protein Subunits; FUNCTIONAL MODULATION; Calcium Channels; BETA SUBUNITS

GABAAreceptors are critical in controlling neuronal activity. Here, we examined the role for phospholipase C-related inactive protein type 1 (PRIP-1), which binds and inactivates protein phosphatase 1α (PP1α) in facilitating GABAAreceptor phospho-dependent regulation usingPRIP-1-/-mice. In wild-type animals, robust phosphorylation and functional modulation of GABAAreceptors containing β3 subunits by cAMP-dependent protein kinase was evident, which was diminished inPRIP-1-/-mice.PRIP-1-/-mice exhibited enhanced PP1α activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABAAreceptor β subunits, and moreover, these proteins were found to be PP1α substrates. Finally, phosphorylation of PRIP-1 on threonine 94 facilitated the dissociation of PP1α-PRIP-1 complexes, providing a local mechanism for the activation of PP1α. Together, these results suggest an essential role for PRIP-1 in controlling GABAAreceptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.