Protein phosphatase-1 inhibitor-2 is a novel memory suppressor

Abstract

Reversible phosphorylation, a fundamental regulatory mechanism required formany biological processes including memory formation, is coordinated By the opposing actions of protein kinases and phosphatases. Type I proteinphosphatase (PP1), in particular, has been shown to constrain learning and Memory formation. However, how PP1might be regulated in memoryis still not clear. Our previous work has elucidated that PP1 inhibitor-2 (I-2) isan Endogenous regulator of PP1 in hippocampal and corticalneurons (Houetal., 2013). Contrary to expectation, our studies of contextual fear conditioning And novel object recognition in I-2heterozygousmicesuggest that I-2 is a memory suppressor. Inaddition, lentiviral knock-down of I-2 in the rat dorsal hippocampus facilitated memory for tasks dependent on the hippocampus. Our data indicate that I-2 suppresses memory formation, probably via negatively regulating the phosphorylation of cAMP/calcium response element-binding protein (CREB) at serine 133 and CREB-mediated gene expression in dorsal hippocampus. Surprisingly, the data from both biochemical and behavioral studies suggest that I-2, despite its assumed action as a PP1 inhibitor, is a positive regulator ofPP1function in memory formation.