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Protein chemistry

X-ray crystallography

Biophysical analysis of protein-protein interactions

Molecular biology

Protein engineering

Yeast surface display

Mammalian protein expression

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Synthetic excitatory synaptic organizer - Science, August 2020

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits

The human brain contains trillions of synapses within a vast network of neurons. Synapse remodeling is essential to ensure the efficient reception and integration of external stimuli and to store and retrieve information. Building and remodeling of synapses occurs throughout life under the control of synaptic organizer proteins. Errors in this process can lead to neuropsychiatric or neurological disorders. Suzuki et al. combined structural elements of natural synaptic organizers to develop an artificial version called CPTX, which has different binding properties (see the Perspective by Salinas). CPTX could act as a molecular bridge to reconnect neurons and restore excitatory synaptic function in animal models of cerebellar ataxia, familial Alzheimer’s disease, and spinal cord injury. The findings illustrate how structure-guided approaches can help to repair neuronal circuits.

Authors: Kunimichi Suzuki, Jonathan Elegheert, Inseon Song, Hiroyuki Sasakura, Oleg Senkov, Keiko Matsuda, Wataru Kakegawa, Amber J. Clayton, Veronica T. Chang, Maura Ferrer-Ferrer, Eriko Miura, Rahul Kaushik, Masashi Ikeno, Yuki Morioka, Yuka Takeuchi, Tatsuya Shimada, Shintaro Otsuka, Stoyan Stoyanov, Masahiko Watanabe, Kosei Takeuchi, Alexander Dityatev, A. Radu Aricescu, Michisuke Yuzaki

- Science, 28 Aug 2020: Vol. 369, Issue 6507, eabb4853 - DOI: 10.1126/science.abb4853
- Contact: Jonathan Elegheert

Jonathan Elegheert is 2022 Laureate FSER

Created on the initiative of a group of scientists wishing to have fundamental research recognised, the Cercle FSER is an association under the French law of 1901. It brings together more than 70 scientists who are committed to fostering the dialogue of science with and for society. To this end, its actions are organised along two main lines: (1) to promote research, its approaches and its challenges to young people, (2) to encourage the involvement of research staff in dialogue with the general public. In 2021, 35,000 people benefited from its actions!

Each year, the Cercle FSER supports young researchers who excel in the field of biomedical research. The candidates are nominated by scientific personalities, former laureates or the CNRS and INSERM. Then, each candidate is selected by a jury on the basis of the quality of his or her past and present scientific research, but also on the basis of his or her performance in the interview.

Thus, Jonathan Elegheert, CNRS scientist (charge de recherches), is one of four laureates of 2022 Cercle FSER! In particular, he obtained the FSER prize, which aims to help young researchers during the first years of their laboratory's creation. This grant enabled Jonathan Elegheert and his team to co-finance a new machine to study protein-protein interactions.

In 2021, Lisa Roux, CNRS research director, was laureate. Like any laureate, the Cercle FSER has enabled her to organise meetings at the Fondation des Treilles! Moreover, as a winner of the Cercle FSER, her objective for 2023 is to participate in the Déclics operation (scientific mediation action with high school students).

One per year, the Cercle FSER organises meetings so that researchers from all disciplines can meet. These exchanges allow them to come up with new and original ideas! The winter meeting took place from 24 to 27 January in Alpe d'Huez. During this meeting, all participants were invited to make a scientific presentation. Thus, Jonathan Elegheert and Lisa Roux intoduced the field of neuroscience! Both presented their research topic: "Structural biology and engineering of neuronal proteins" for Jonathan Elegheert and "Olfaction and Memory" for Lisa Roux.

Would you like to know more? Nolwenn Cloarec, communication officer: nolwenn.cloarec@u-bordeaux.fr

Selected Publications

Suzuki K*, Elegheert J*, Song I*, Sasakura H*, Senkov O, Matsuda K, Kakegawa W, Clayton AJ, Chang VT, Ferrer-Ferrer M, Miura E, Kaushik R, Ikeno M, Morioka Y, Takeuchi Y, Shimada T, Otsuka S, Stoyanov S, Watanabe M, Takeuchi K, Dityatev A, Aricescu AR, Yuzaki M.

A synthetic synaptic organizer protein restores glutamatergic neuronal circuits Science (2020)
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Connor SA, Elegheert J, Xie Y, Craig AM.

Pumping the brakes: suppression of synapse development by MDGA-neuroligin interactions Current Opinion in Neurobiology (2019)
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Elegheert J, Behiels E, Bishop B, Scott S, Woolley RE, Griffiths SC, Byrne EFX, Chang VT, Stuart DI, Jones EY, Siebold C, Aricescu AR.

Lentiviral transduction of mammalian cells for fast, scalable and high-level production of soluble and membrane proteins Nature Protocols (2018)
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Elegheert J, Cvetkovska V, Clayton AJ, Heroven C, Vennekens KM, Smukowski SN, Regan MC, Jia W, Smith AC, Furukawa H, Savas JN, de Wit J, Begbie J, Craig AM, Aricescu AR.

Structural Mechanism for Modulation of Synaptic Neuroligin-Neurexin Signaling by MDGA Proteins Neuron (2017)
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Elegheert J, Kakegawa W, Clay JE, Shanks NF, Behiels E, Matsuda K, Kohda K, Miura E, Rossmann M, Mitakidis N, Motohashi J, Chang VT, Siebold C, Greger IH, Nakagawa T, Yuzaki M, Aricescu AR.

Structural basis for integration of GluD receptors within synaptic organizer complexes Science (2016)
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