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The University of Southampton
Biological Sciences

Dynamics and Consequences of Regulating mRNA Translation at the Elongation Phase in Neurons in the Context of Memory Formation ***PLEASE NOTE THE CHANGE OF VENUE*** Seminar

13:00 - 14:00
13 May 2014
34/3001 - please note the change of venue

For more information regarding this seminar, please telephone Kim Lipscombe on 02380 59 7747 or email .

Event details

Numerous aspects of neurophysiology, such as learning and memory, are modulated by calcium-coordinated regulation of cell signalling cascades. For example, the elongation phase of mRNA translation, one of the most energy intensive processes in cells, is regulated by the calcium/calmodulin dependent elongation factor 2 kinase (eEF2k). Furthermore, recent work has found that modifying eEF2k function results in learning and memory deficits in mice. However, little is known about both the dynamics of eEF2k regulation, and the consequences of modulating eEF2k function.

  • To determine the network of biochemical interactions necessary to describe the calcium-coordinated dynamics of eEF2k regulation in neurons, we used a combination of pharmacological, biochemical, and mathematical modelling approaches. In doing so, we both  identified the minimal biochemical network required to explain eEF2k regulatory dynamics in neurons, and  generated the first mathematical model of eEF2k regulation.
  • Altering mRNA translation at the elongation phase via the modulation of eEF2k activity has been proposed to result in the increased synthesis of specific plasticity related proteins. However, with the exception of a few well characterized examples, the identities of these elongation regulated proteins, and how this regulation is conferred, remains largely unknown. To determine the proteins whose synthesis is regulated via elongation in an unbiased manner in primary neurons, we developed a novel mass spectrometry based approach in which we combined click-chemistry and SILAC (stable isotope labelling of amino acids in cell culture). Using this approach, we identified several novel candidates for regulation by eEF2k, and find that these candidates tend to be involved in modulating microtubule function.
  • These findings are discussed in the context of neurophysiology, with a focus on how they may be important for understanding the contribution that the regulation of protein synthesis makes to memory consolidation.

Speaker information

Justin Kenney

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