Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: EC:2.7.11.17 (
CaMKII
)
4,029
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
GABAergic dysfunction underlies many neurodevelopmental and psychiatric disorders. GABAergic synapses exhibit several forms of plasticity at both pre- and postsynaptic levels. NMDA receptor (NMDAR)-dependent inhibitory long-term potentiation (iLTP) at GABAergic postsynapses requires an increase in surface GABA
A
Rs through promoted exocytosis; however, the regulatory mechanisms and the neuropathological significance remain unclear. Here we report that the autism-related protein PX-
RICS
is involved in GABA
A
R transport driven during NMDAR-dependent GABAergic iLTP. Chemically induced iLTP elicited a rapid increase in surface GABA
A
Rs in wild-type mouse hippocampal neurons, but not in PX-
RICS
/
RICS
-deficient neurons. This increase in surface GABA
A
Rs required the PX-
RICS
/GABARAP/14-3-3 complex, as revealed by gene knockdown and rescue studies. iLTP induced
CaMKII
-dependent phosphorylation of PX-
RICS
to promote PX-
RICS
-14-3-3 assembly. Notably, PX-
RICS
/
RICS
-deficient mice showed impaired amygdala-dependent fear learning, which was ameliorated by potentiating GABAergic activity with clonazepam. Our results suggest that PX-
RICS
-mediated GABA
A
R trafficking is a key target for GABAergic plasticity and its dysfunction leads to atypical emotional processing underlying autism.
...
PMID:The Autism-Related Protein PX-RICS Mediates GABAergic Synaptic Plasticity in Hippocampal Neurons and Emotional Learning in Mice. 3004 17
