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pubmed:abstractText |
Disturbances in GABA(A) receptor trafficking contribute to several neurological and psychiatric disorders by altering inhibitory neurotransmission. Identifying mechanisms that regulate GABA(A) receptor trafficking could lead to better understanding of disease pathogenesis and treatment. Here, we show that protein kinase C? (PKC?) regulates the N-ethylmaleimide-sensitive factor (NSF), an ATPase critical for membrane fusion events, and thereby promotes the trafficking of GABA(A) receptors. Activation of PKC? decreased cell surface expression of GABA(A) receptors and attenuated GABA(A) currents. Activated PKC? associated with NSF, phosphorylated NSF at serine 460 and threonine 461, and increased NSF ATPase activity, which was required for GABA(A) receptor downregulation. These findings identify new roles for NSF and PKC? in regulating synaptic inhibition through downregulation of GABA(A) receptors. Reducing NSF activity by inhibiting PKC? could help restore synaptic inhibition in disease states in which it is impaired.
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