The Department of Biomedicine

BBB seminar: David G. Wells

Exploring a role for "local" protein synthesis in synaptic plasticity, learning and memory

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David G. Wells
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT, USA

Information is transmitted in the nervous system through specialized connections called synapses. Neurons can receive thousands of synapses, potentially from thousands of different neurons; yet, remarkably, each synapse can be modified - the strength of the signal can be increased or decreased - independently. This ability is widely thought to be the cellular encoding of information or memory. Long-term changes in synaptic strength (plasticity) are dependent upon synthesis of new proteins and there is growing evidence that a cohort of mRNAs appear to be translated locally at or near the synapse. Some dendritically targeted mRNAs contain cytoplasmic polyadenylation element (CPE) sequences in their 3' untranslated region (UTR). The trans-acting CPE-binding protein CPEB may mediate the translation of these mRNAs. This talk will address the evidence that CPEB is involved in neuronal function and focus on new results that suggest that CPEB-mediated protein synthesis plays an important role in Purkinje neuron synaptic plasticity and cerebellar function.

Host: Clive Bramham, Department of Biomedicine

David Wells, Assistant Professor at Yale University, is a leading scientist in the burgeoning new area of dendritic protein synthesis. His work focuses on the molecular mechanism regulating mRNA translation in dendrites. His research has shown that this process depends on an mRNA binding protein called CPEB that is present in neurons and localized to synapses. CPEB was first described in Xenopus oocytes where it regulates mRNA translation through poly(A) tail elongation. David Wells has demonstrated polyadenylation-dependent translation of specific messages in the visual cortex and hippocampus. Such mechanisms are considered important for a range of long-term adaptive responses such as synapse formation in brain development and synapse strengthening during memory storage.