Abstract
GABAA receptors 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 GABAA receptor phospho-dependent regulation using PRIP-1-/- mice. In wild-type animals, robust phosphorylation and functional modulation of GABAA receptors containing β3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1-/- mice. PRIP-1-/- mice exhibited enhanced PP1α activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABAA receptor 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 GABAA receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.
| Original language | English |
|---|---|
| Pages (from-to) | 7074-7084 |
| Number of pages | 11 |
| Journal | Journal of Neuroscience |
| Volume | 24 |
| Issue number | 32 |
| DOIs | |
| Publication status | Published - Aug 11 2004 |
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All Science Journal Classification (ASJC) codes
- Neuroscience(all)
Cite this
GABAA receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein. / Terunuma, Miho; Jang, Il Sung; Ha, Sang Hoon; Kittler, Josef T.; Kanematsu, Takashi; Jovanovic, Jasmina N.; Nakayama, Keiichi I.; Akaike, Norio; Ryu, Sung Ho; Moss, Stephen J.; Hirata, Masato.
In: Journal of Neuroscience, Vol. 24, No. 32, 11.08.2004, p. 7074-7084.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - GABAA receptor phospho-dependent modulation is regulated by phospholipase C-related inactive protein type 1, a novel protein phosphatase 1 anchoring protein
AU - Terunuma, Miho
AU - Jang, Il Sung
AU - Ha, Sang Hoon
AU - Kittler, Josef T.
AU - Kanematsu, Takashi
AU - Jovanovic, Jasmina N.
AU - Nakayama, Keiichi I.
AU - Akaike, Norio
AU - Ryu, Sung Ho
AU - Moss, Stephen J.
AU - Hirata, Masato
PY - 2004/8/11
Y1 - 2004/8/11
N2 - GABAA receptors 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 GABAA receptor phospho-dependent regulation using PRIP-1-/- mice. In wild-type animals, robust phosphorylation and functional modulation of GABAA receptors containing β3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1-/- mice. PRIP-1-/- mice exhibited enhanced PP1α activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABAA receptor 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 GABAA receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.
AB - GABAA receptors 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 GABAA receptor phospho-dependent regulation using PRIP-1-/- mice. In wild-type animals, robust phosphorylation and functional modulation of GABAA receptors containing β3 subunits by cAMP-dependent protein kinase was evident, which was diminished in PRIP-1-/- mice. PRIP-1-/- mice exhibited enhanced PP1α activity compared with controls. Furthermore, PRIP-1 was able to interact directly with GABAA receptor 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 GABAA receptor activity via regulating subunit phosphorylation and thereby the efficacy of neuronal inhibition mediated by these receptors.
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UR - http://www.scopus.com/inward/citedby.url?scp=4143067020&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.1323-04.2004
DO - 10.1523/JNEUROSCI.1323-04.2004
M3 - Article
C2 - 15306641
AN - SCOPUS:4143067020
VL - 24
SP - 7074
EP - 7084
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 32
ER -