RP9: Ubiquitylation-controlled Arc/Arg3.1 translation and protein turnover in synaptic plasticity and memory consolidation

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Enduring forms of synaptic plasticity and long-term memory are dependent on gene transcription and protein synthesis. A specific example can be seen in the expression of Arc/Arg3.1 which is essential for the consolidation of synaptic plasticity and memories. Upon plasticity-producing stimulation Arc/Arg3.1 mRNA is induced and targeted to dendrites. Within dendrites Zinki, an mRNA binding protein that acts as a repressor of Arc/Arg3.1 translation, becomes degraded via the ubiquitin/proteasome system. Besides activity-dependent relief of translational repression, Arc/Arg3.1 protein has a short halflife, suggesting additional regulation of Arc/Arg3.1 by protein turnover. We will ask the following questions: i) how translational control of Arc/Arg3.1 mRNA is exerted by the dendritic mRNA binding protein Zinki, ii) determine how activity-dependent ubiquitylation and proteasomal degradation of Zinki might contribute to synaptic input specificity, iii) define the molecular pathways that control Arc/Arg3.1 protein turnover and iv) ask what functional consequence these bear on AMPA receptor trafficking, homeostasis, plasticity, and memory.