A decrease in eukaryotic elongation factor 2 phosphorylation is required for local translation of sensorin and long‐term facilitation in Aplysia

Mechanistic target of rapamycin complex 1 ( mTORC 1)‐dependent protein synthesis is required for many forms of synaptic plasticity and memory, but the downstream pathways important for synaptic plasticity are poorly understood. Long‐term facilitation ( LTF ) in Aplysia is a form of synaptic plasticity that is closely linked to behavioral memory and an attractive model system for examining the important downstream targets for mTORC 1 in regulating synaptic plasticity. Although mTORC 1‐regulated protein synthesis has been strongly linked to translation initiation, translation elongation is also regulated by mTORC 1 and LTF leads to an mTORC 1‐dependent decrease in eukaryotic elongation factor 2 ( eEF 2) phosphorylation. The purpose of this study is to test the hypothesis that the decrease in eEF 2 phosphorylation is required for mTORC 1‐dependent translation and plasticity. We show that the LTF ‐induced decrease in eEF 2 phosphorylation is blocked by expression of an eEF 2 kinase ( eEF 2K) modified to be resistant to mTORC 1 regulation. We found that expression of this modified kinase blocked LTF . LTF requires local protein synthesis of the neuropeptide sensorin and importantly, local sensorin synthesis can be measured using a dendra fluorescent protein containing the 5′ and 3′ untranslated regions ( UTR s) of sensorin. Using this construct, we show that blocking eEF 2 dephosphorylation also blocks the increase in local sensorin synthesis. These results identify decreases in eEF 2 phosphorylation as a critical downstream effector of mTOR required for long‐term plasticity and identify an important translational target regulated by decreases in eEF 2 phosphorylation.