• BMB Reports
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• v.46 no.2
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• pp.103-106
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• 2013

Phosphoinositide 3-kinases (PI3Ks) play key roles in synaptic plasticity and cognitive functions in the brain. We recently found that genetic deletion of $PI3K{\gamma}$, the only known member of class IB PI3Ks, results in impaired N-methyl-D-aspartate receptor-dependent long-term depression (NMDAR-LTD) in the hippocampus. The activity of RalA, a small GTP-binding protein, increases following NMDAR-LTD inducing stimuli, and this increase in RalA activity is essential for inducing NMDAR-LTD. We found that RalA activity increased significantly in $PI3K{\gamma}$ knockout mice. Furthermore, NMDAR-LTD-inducing stimuli did not increase RalA activity in $PI3K{\gamma}$ knockout mice. These results suggest that constitutively increased RalA activity occludes further increases in RalA activity during induction of LTD, causing impaired NMDAR-LTD. We propose that $PI3K{\gamma}$ regulates the activity of RalA, which is one of the molecular mechanisms inducing NMDAR-dependent LTD.