title: Elevated RalA activity in the hippocampus of PI3Kγ knock-out mice lacking NMDAR-dependent long-term depression.
abstract: Phosphoinositide 3-kinases (PI3Ks) play key roles in synaptic plasticity and cognitive functions in the brain. We recently found that genetic deletion of PI3Kγ, 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 PI3Kγ knockout mice. Furthermore, NMDAR-LTD-inducing stimuli did not increase RalA activity in PI3Kγ 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 PI3Kγ regulates the activity of RalA, which is one of the molecular mechanisms inducing NMDAR dependent LTD.
authors: Department of Brain and Cognitive Sciences, College of Natural Sciences, Seoul National University, Seoul 151-747, Korea.
authors: Su-Eon
authors: SE
authors: Sim
authors: Hye-Ryeon
authors: HR
authors: Lee
authors: Jae-Ick
authors: JI
authors: Kim
authors: Sun-Lim
authors: SL
authors: Choi
authors: Joseph
authors: J
authors: Bakes
authors: Deok-Jin
authors: DJ
authors: Jang
authors: Kyungmin
authors: K
authors: Lee
authors: Kihoon
authors: K
authors: Han
authors: Eunjoon
authors: E
authors: Kim
authors: Bong-Kiun
authors: BK
authors: Kaang
mesh_terms: D000818:Animals; D058544:Class Ib Phosphatidylinositol 3-Kinase / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D003863:Depression / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009473:Neuronal Plasticity; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D020725:ral GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D016194:Receptors, N-Methyl-D-Aspartate; D058544:Class Ib Phosphatidylinositol 3-Kinase; C546764:Pik3cg protein, mouse; C118120:Rala protein, mouse; D020725:ral GTP-Binding Proteins