Proteins catalyse most of the reactions in the cell on which life depends, thus a large proportion of the cell’s energy resources are devoted to protein synthesis, a key step of which is mRNA translation. Translational control is defined as a change in protein production per mRNA per unit of time, and it is a powerful means to alter protein abundance.

 

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Signalling Pathways upstream of translation

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Our lab is particularly interested in understanding the molecular and signalling mechanisms of translational control in the brain and how they control complex brain functions and behaviours, such as learning, memory, social interactions, anxiety and fear.

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Using biochemical, electrophysiological and behavioural analysis in rodents, we wish to examine translational control as a key tenet in the pathophysiology of neuropsychiatric/ neurodevelopmental disorders such as Autism Spectrum Disorders (ASD), Fragile X Syndrome (FXS) and Intellectual Disability (ID).

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Publications

2017

Gantois I., Khoutorsky A., Popic J., Freemantle E., Aguilar-Valles A., Cao R., Sharma V., Nagpal A., Gamache K., Chapat C., Pooters T., Nader K., Lacaille J. C., Sonenberg N.* and Gkogkas C. G.* Metformin ameliorates core deficits in a Fragile X syndrome mouse model. Nature Medicine doi: 10.1038/nm.4335 (2017) *co-last author

 

Tuttle A. H., Tansley S., Dossett K., Tohyama S., Khoutorsky A., Maldonado-Bouchard S., Stein L., Gerstein L., Crawhall-Duk H., Pearl R., Sukosd M., Leger P., Hardt O., Yachnin D., Austin J. S., Chan C. M., Groves I., Pooters T., Martin L. J., Sonenberg N., Mogil J. S.* & Gkogkas C. G.* Social propinquity in rodents as measured by tube co-occupancy differs between inbred and outbred genotypes PNAS doi: 10.1073/pnas.1703477114 (2017) *co-last author

 

Chapat C., Jafarnejad S. M., Matta-Camacho E., Hesketh G. G., Gelbart I. A., Attig J., Gkogkas C. G., Alain T., Stern-Ginossar N., Fabian M. R., Gingras A. C., Duchaine T. F. and Sonenberg N. Cap-binding protein 4EHP effects translation silencing by microRNAs PNAS doi: 10.1073/pnas.1701488114  (2017)

 

2016

Tahmasebi S., Jafarnejad S. M., Tam I. S., Gonatopoulos-Pournatzis T., Matta-Camacho E., Tsukumo Y., Yanagiya A., Li W., Atlasi Y., Caron M., Braunschweig U., Pearl D., Khoutorsky A., Gkogkas C. G., Nadon R., Bourque G., Yang X. J., Tian B., Stunnenberg H. G., Yamanaka Y., Blencowe B. J., Giguère V., & Sonenberg N. Control of embryonic stem cells self-renewal and differentiation via coordinated splicing and translation of YY2. PNAS doi: 10.1073/pnas.1615540113 (2016)

 

Khoutorsky, A., Sorge R.E., Prager-Khoutorsky M., Pawlowski S. A., Longod G., Jafarnejad S. M., Tahmasebi S., Martin L., Pitchere M. H., Gkogkas C. G., Sharif-Naeinig R., Alfredo Ribeiro-da-Silvad A., Bourque C. W., Cerveroh F., Mogil J. S., & Sonenberg N. eIF2alpha phosphorylation controls thermal nociception. PNAS doi: 10.1073/pnas.1614047113 (2016)

 

Skalecka, A., Liszewska, E., Bilinski, R., Gkogkas, C., Khoutorsky, A., Malik, A. R., Sonenberg, N. & Jaworski, J. mTOR kinase is needed for the development and stabilization of dendritic arbors in newly born olfactory bulb neurons. Dev Neurobiol, doi:10.1002/dneu.22392 (2016).

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2015

Khoutorsky, A., Bonin, R. P., Sorge, R. E., Gkogkas, C. G., Pawlowski, S. A., Jafarnejad, S. M., Pitcher, M. H., Alain, T., Perez-Sanchez, J., Salter, E. W., Martin, L., Ribeiro-da-Silva, A., De Koninck, Y., Cervero, F., Mogil, J. S. & Sonenberg, N. Translational control of nociception via 4E-binding protein 1. Elife 4, doi:10.7554/eLife.12002 (2015).

 

Maity, S., Rah, S., Sonenberg, N., Gkogkas, C. G. & Nguyen, P. V. Norepinephrine triggers metaplasticity of LTP by increasing translation of specific mRNAs. Learn Mem 22, 499-508, doi:10.1101/lm.039222.115 (2015).

 

Aguilar-Valles, A., Matta-Camacho, E., Khoutorsky, A., Gkogkas, C., Nader, K., Lacaille, J. C. & Sonenberg, N. Inhibition of Group I Metabotropic Glutamate Receptors Reverses Autistic-Like Phenotypes Caused by Deficiency of the Translation Repressor eIF4E Binding Protein 2. The Journal of neuroscience : the official journal of the Society for Neuroscience 35, 11125-11132, doi:10.1523/JNEUROSCI.4615-14.2015 (2015).

 

Cao, R., Gkogkas, C. G., de Zavalia, N., Blum, I. D., Yanagiya, A., Tsukumo, Y., Xu, H., Lee, C., Storch, K. F., Liu, A. C., Amir, S. & Sonenberg, N. Light-regulated translational control of circadian behavior by eIF4E phosphorylation. Nature Neuroscience 18, 855-862, doi:10.1038/nn.4010 (2015).

 

Aulas, A., Caron, G., Gkogkas, C. G., Mohamed, N. V., Destroismaisons, L., Sonenberg, N., Leclerc, N., Parker, J. A. & Vande Velde, C. G3BP1 promotes stress-induced RNA granule interactions to preserve polyadenylated mRNA. J Cell Biol 209, 73-84, doi:10.1083/jcb.201408092 (2015).

 

2014

Gkogkas, C. G., Khoutorsky, A., Cao, R., Jafarnejad, S. M., Prager-Khoutorsky, M., Giannakas, N., Kaminari, A., Fragkouli, A., Nader, K., Price, T. J., Konicek, B. W., Graff, J. R., Tzinia, A. K., Lacaille, J. C. & Sonenberg, N. Pharmacogenetic inhibition of eIF4E-dependent Mmp9 mRNA translation reverses fragile X syndrome-like phenotypes. Cell reports 9, 1742-1755, doi:10.1016/j.celrep.2014.10.064 (2014).

 

Jung, H., Gkogkas, C. G., Sonenberg, N. & Holt, C. E. Remote control of gene function by local translation. Cell 157, 26-40, doi:10.1016/j.cell.2014.03.005 (2014).

 

Tahmasebi, S., Alain, T., Rajasekhar, V. K., Zhang, J. P., Prager-Khoutorsky, M., Khoutorsky, A., Dogan, Y., Gkogkas, C. G., Petroulakis, E., Sylvestre, A., Ghorbani, M., Assadian, S., Yamanaka, Y., Vinagolu-Baur, J. R., Teodoro, J. G., Kim, K., Yang, X. J. & Sonenberg, N. Multifaceted regulation of somatic cell reprogramming by mRNA translational control. Cell Stem Cell 14, 606-616, doi:10.1016/j.stem.2014.02.005 (2014).

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2013

Gkogkas, C. G. & Sonenberg, N. Translational control and autism-like behaviors. Cell Logist 3, e24551, doi:10.4161/cl.24551 (2013).

 

Cao, R., Robinson, B., Xu, H., Gkogkas, C., Khoutorsky, A., Alain, T., Yanagiya, A., Nevarko, T., Liu, A. C., Amir, S. & Sonenberg, N. Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron 79, 712-724, doi:10.1016/j.neuron.2013.06.026 (2013).

 

Khoutorsky, A., Gkogkas, C. G.*, Yanagiya, A.*, Fabian, M. R., Prager-Khoutorsky, M., Cao, R., Gamache, K., Bouthiette, F., Parsyan, A., Sorge, R. E., Mogil, J. S., Nader, K., Lacaille, J. C. & Sonenberg, N. Control of synaptic plasticity and memory via suppression of poly(A)-binding protein. Neuron 78, 298-311, doi:10.1016/j.neuron.2013.02.025 (2013).

 

Ran, I., Gkogkas, C. G., Vasuta, C., Tartas, M., Khoutorsky, A., Laplante, I., Parsyan, A., Nevarko, T., Sonenberg, N. & Lacaille, J. C. Selective regulation of GluA subunit synthesis and AMPA receptor-mediated synaptic function and plasticity by the translation repressor 4E-BP2 in hippocampal pyramidal cells. The Journal of neuroscience : the official journal of the Society for Neuroscience 33, 1872-1886, doi:10.1523/JNEUROSCI.3264-12.2013 (2013).

 

Gkogkas, C. G., Khoutorsky, A., Ran, I., Rampakakis, E., Nevarko, T., Weatherill, D. B., Vasuta, C., Yee, S., Truitt, M., Dallaire, P., Major, F., Lasko, P., Ruggero, D., Nader, K., Lacaille, J. C. & Sonenberg, N. Autism-related deficits via dysregulated eIF4E-dependent translational control. Nature 493, 371-377, doi:10.1038/nature11628 (2013).

 

2003-2012

Chua, J. J., Schob, C., Rehbein, M., Gkogkas, C. G., Richter, D. & Kindler, S. Synthesis of two SAPAP3 isoforms from a single mRNA is mediated via alternative translational initiation. Sci Rep 2, 484, doi:10.1038/srep00484 (2012).

 

Parsyan, A., Svitkin, Y., Shahbazian, D., Gkogkas, C., Lasko, P., Merrick, W. C. & Sonenberg, N. mRNA helicases: the tacticians of translational control. Nat Rev Mol Cell Biol 12, 235-245, doi:10.1038/nrm3083 (2011).

 

Gkogkas, C., Wardrope, C., Hannah, M. & Skehel, P. The ALS8-associated mutant VAPB(P56S) is resistant to proteolysis in neurons. J Neurochem 117, 286-294, doi:10.1111/j.1471-4159.2011.07201.x (2011).

 

Gkogkas, C., Sonenberg, N. & Costa-Mattioli, M. Translational control mechanisms in long-lasting synaptic plasticity and memory. J Biol Chem 285, 31913-31917, doi:10.1074/jbc.R110.154476 (2010).

 

Bidinosti, M., Ran, I., Sanchez-Carbente, M. R., Martineau, Y., Gingras, A. C., Gkogkas, C., Raught, B., Bramham, C. R., Sossin, W. S., Costa-Mattioli, M., DesGroseillers, L., Lacaille, J. C. & Sonenberg, N. Postnatal deamidation of 4E-BP2 in brain enhances its association with raptor and alters kinetics of excitatory synaptic transmission. Mol Cell 37, 797-808, doi:10.1016/j.molcel.2010.02.022 (2010).

 

Rampakakis, E., Gkogkas, C., Di Paola, D. & Zannis-Hadjopoulos, M. Replication initiation and DNA topology: The twisted life of the origin. J Cell Biochem 110, 35-43, doi:10.1002/jcb.22557 (2010).

 

Gkogkas, C., Middleton, S., Kremer, A. M., Wardrope, C., Hannah, M., Gillingwater, T. H. & Skehel, P. VAPB interacts with and modulates the activity of ATF6. Hum Mol Genet 17, 1517-1526, doi:10.1093/hmg/ddn040 (2008).

 

Gkogkas, C. G.*, Vernikos, G. S.*, Promponas, V. J. & Hamodrakas, S. J. GeneViTo: visualizing gene-product functional and structural features in genomic datasets. BMC Bioinformatics 4, 53, doi:10.1186/1471-2105-4-53 (2003). *co-first

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