Protein Phosphatase-1 Inhibitor-2 Is a Novel Memory Suppressor

• DOI: 10.1523/jneurosci.1865-15.2015
• Publication Date: 2015-11-11T17:28:41Z
• Authors: Hongtian Yang; Hailong Hou; Amanda Pahng; Hua Gu; Angus C. Nairn; Ya-Ping Tang; Paul J. Colombo; Houhui Xia
• Keywords: Protein phosphatase 1; CREB-binding protein

Reversible phosphorylation, a fundamental regulatory mechanism required for many biological processes including memory formation, is coordinated by the opposing actions of protein kinases and phosphatases. Type I phosphatase (PP1), in particular, has been shown to constrain learning formation. However, how PP1 might be regulated still not clear. Our previous work elucidated that inhibitor-2 (I-2) an endogenous regulator hippocampal cortical neurons (Hou et al., 2013). Contrary expectation, our studies contextual fear conditioning novel object recognition I-2 heterozygous mice suggest suppressor. In addition, lentiviral knock-down rat dorsal hippocampus facilitated tasks dependent on hippocampus. data indicate suppresses probably via negatively regulating phosphorylation cAMP/calcium response element-binding (CREB) at serine 133 CREB-mediated gene expression Surprisingly, from both biochemical behavioral I-2, despite its assumed action as inhibitor, positive function SIGNIFICANCE STATEMENT We found acts suppressor through functional influence type likely resulting negative regulation CREB-activated expression. thus provide interesting example molecule with vivo opposite vitro function. plays critical roles essential physiological functions such cell mitosis glucose metabolism addition known role pharmacological inhibitors would able serve good therapeutic reagents because targets. identification contributor suppression formation may target memory-related diseases.