Protein phosphatase 1-dependent transcriptional programs for long-term memory and plasticity.
Gene transcription is essential for the establishment and the maintenance of long-term memory (LTM) and for long-lasting forms of synaptic plasticity. The molecular mechanisms that control gene transcription in neuronal cells are complex and recruit multiple signaling pathways in the cytoplasm and the nucleus. Protein kinases (PKs) and phosphatases (PPs) are important players in these mechanisms. Protein serine/threonine phosphatase 1 (PP1), in particular, was recently shown to be important for transcription-dependent memory by regulating chromatin remodeling. However, the impact of PP1 on gene transcription in adult neurons remains not fully delineated. Here, we demonstrate that the nuclear pool of PP1 is associated with transcriptional events involving molecular components of signaling cascades acting as positive and negative regulators of memory and brain plasticity. The data show that inhibiting this pool selectively in forebrain neurons improves memory performance, enhances long-term potentiation (LTP), and modulates gene transcription. These findings highlight an important role for PP1 in the regulation of gene transcription in LTM and synaptic plasticity in the adult brain.
Gräff
Johannes
J
Brain Research Institute, Medical Faculty of University Zürich and Department of Biology of Swiss Federal Institute of Technology, CH-8057 Zürich, Switzerland.
Koshibu
Kyoko
K
Jouvenceau
Anne
A
Dutar
Patrick
P
Mansuy
Isabelle M
IM
D000818:Animals; D002467:Cell Nucleus / Q000378:metabolism; D015870:Gene Expression; D005786:Gene Expression Regulation / Q000502:physiology*; D006624:Hippocampus / Q000502:physiology*; D017774:Long-Term Potentiation / Q000502:physiology; D008568:Memory / Q000502:physiology*; D051379:Mice; D008822:Mice, Transgenic; D009473:Neuronal Plasticity / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D054645:Protein Phosphatase 1 / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D014158:Transcription, Genetic
D054645:Protein Phosphatase 1