Control of neuronal protein homeostasis (proteostasis) is critical under both normal and abnormal synaptic function. Neuronal synapses possess 100-500 protein species that range in their copy number at individual synapses from 10-100+ copies. In order to maintain synaptic function it is clear that there must be tight regulation of protein synthesis, degradation and trafficking. In neuronal dendrites, the machinery for both protein synthesis and degradation is present in or close to the synaptic cleft, endowing them with the capacity for local alterations in the proteome. Indeed, it is well-established that some forms of synaptic plasticity require local protein synthesis or protein degradation. The main objective of this project is to clarify the cross-talks between protein synthesis and degradation in neurons, since these two cellular processes have to be coordinated for keeping proteostasis since they have mostly been studied independently. The experimental approach will include manipulating protein synthesis and degradation globally and locally (dendrites) in dissociated neurons and brain slices. I will also study the changes in protein synthesis and degradation in response to different synaptic plasticity paradigms, centered in the hippocampus. These studies will certainly contribute to a better understanding of the molecular mechanism responsible of proteostasis in neurons and its role in normal neuronal function, neuronal plasticity and will have clear implications to understand disease.
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