We found that Numb directly binds to p120. Numb depletion impaired E-cadherin internalization. aPKC phosphorylated Numb and inhibited its association with p120. In the Numb-depleted cells, the phosphomimetic Numb mutant failed to restore E-cadherin internalization. We propose the mode of action of Numb for intercellular adhesion downstream of aPKC.
The effects of nefiracetam, [N-(2,6-dimethyl-phenyl)-2-(2-oxo-pyrrolidinyl)acetamide, DM-9384], a cyclic derivative of GABA, were investigated in the cycloheximide (CXM)-induced amnesia animal model using the passive avoidance task. Pre-training administration of DM-9384 attenuated the CXM-induced amnesia as indicated by prolongation of step-down latency. It protected against CXM-induced inhibition of choline acetyltransferase activity in the cerebral cortex. These results suggest that DM-9384 attenuates CXM-induced amnesia by interacting with AChergic neuronal system and enhancing protein synthesis in the brain.
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