Current studentsExisting staffContact us
 

Bicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1-dependent phosphorylation

Simple item page
dc.contributor.authorGladulich, L.F.H.
dc.contributor.authorXie, J.
dc.contributor.authorJensen, K.B.
dc.contributor.authorKamei, M.
dc.contributor.authorPaes-de-Carvalho, R.
dc.contributor.authorCossenza, M.
dc.contributor.authorProud, C.G.
dc.date.issued2020
dc.description.abstractThe regulation of protein synthesis is a vital and finely tuned process in cellular physiology. In neurons, this process is very precisely regulated, as which mRNAs undergo translation is highly dependent on context. One of the most prominent regulators of protein synthesis is the enzyme eukaryotic elongation factor kinase 2 (eEF2K) regulates the elongation stage of protein synthesis. This kinase and its substrate, eukaryotic elongation factor 2 (eEF2) are important in processes such as neuronal development and synaptic plasticity. eEF2K is regulated by multiple mechanisms including Ca2+ -ions and the mTORC1 signaling pathway, both of which play key roles in neurological processes such as learning and memory. In such settings, the localized control of protein synthesis is of crucial importance. In this work, we sought to investigate how the localization of eEF2K is controlled and the impact of this on protein synthesis in neuronal cells. In this study, we used both SH-SY5Y neuroblastoma cells and mouse cortical neurons, and pharmacologically and/or genetic approaches to modifying eEF2K function. We show that eEF2K activity and localization can be regulated by its binding partner Homer1b/c, a scaffolding protein known for its participation in calcium-regulated signaling pathways. Furthermore, our results indicate that this interaction is regulated by the mTORC1 pathway, through a known phosphorylation site in eEF2K (S396), and that it affects rates of localized protein synthesis at synapses depending on the presence or absence of this scaffolding protein.
dc.identifier.citationJournal of Neurochemistry, 2020; 157(4):1086-1107
dc.identifier.doi10.1111/jnc.15178
dc.identifier.issn0022-3042
dc.identifier.issn1471-4159
dc.identifier.orcidJensen, K.B. [0000-0002-2084-1734]
dc.identifier.orcidKamei, M. [0000-0002-1438-0783]
dc.identifier.orcidProud, C.G. [0000-0003-0704-6442]
dc.identifier.urihttps://hdl.handle.net/11541.2/144762
dc.language.isoen
dc.publisherWiley
dc.relation.fundingSouth Australian Health and Medical Research Institute
dc.relation.fundingFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado E-26/202.966/2017
dc.relation.fundingFundação Carlos Chagas Filho de Amparo à Pesquisa do Estado E-26/010.101037/2018
dc.relation.fundingCoordenação de Aperfeiçoamento de Pessoal de Nível Superior PDSE - 88881.188435/2018-01
dc.relation.fundingCoordenação de Aperfeiçoamento de Pessoal de Nível Superior 88882.456039/2019-01
dc.relation.fundingConselho Nacional de Desenvolvimento Científico e Tecnológico CNPq 303101/2015-6
dc.relation.fundingConselho Nacional de Desenvolvimento Científico e Tecnológico 426687/2018-3
dc.rightsCopyright 2020 International Society for Neurochemistry
dc.source.urihttps://doi.org/10.1111/jnc.15178
dc.subjecteEF2K
dc.subjectHomer1
dc.subjectmTORC1
dc.subjectProtein Synthesis
dc.subjectSynapse
dc.titleBicuculline regulated protein synthesis is dependent on Homer1 and promotes its interaction with eEF2K through mTORC1-dependent phosphorylation
dc.typeJournal article
pubs.publication-statusPublished
ror.mmsid9916453611001831

Files

Collections