Cytoplasmic Polyadenylation Element Binding Protein 1-Mediated mRNA Translation in Purkinje Neurons Is Required for Cerebellar Long-Term Depression and Motor Coordination

• DOI: 10.1523/jneurosci.5211-06.2007
• Publication Date: 2007-06-14T05:09:30Z
• Authors: M. McEvoy; G. Cao; P. M. Llopis; M. Kundel; K. Jones; C. Hofler; C. Shin; D. G. Wells
• Keywords: Motor coordination; Depression; Long-term depression

The ability of neurons to modify synaptic connections is critical for proper brain development and function in the adult. It now clear that changes strength are often accompanied by morphology. This plasticity can be maintained varying lengths time depending on type neuronal activity first induced changes. Long-term requires synthesis new proteins, one mechanism regulation experience-induced protein involves cytoplasmic polyadenylation element binding (CPEB1). CPEB1 bidirectionally regulate mRNA translation, repressing then activating translation after phosphorylation two residues (T171 S177). To determine full extent CPEB1-mediated function, we engineered a line mice expressing with these sites mutated alanines (mCPEB1-AA) exclusively cerebellar Purkinje (PNs). Thus, mRNAs bound mCPEB1-AA would held translationally dormant state. We show localizes synapses cerebellum resulted loss synthesis-dependent phase parallel fiber-PN long-term depression. was change spine number length likely attributable part dysregulation IRSp53, known play role structure. Finally, displayed significant impairment motor coordination learning delay.