The discovery of the role of β-arrestins in the formation of the spinal cord at the embryonic stage opens up perspectives for exploring the mechanisms that would allow its lesions to be repaired. Understanding the complex mechanisms of nervous system development still has many gray areas, which hinders the development of effective therapies to promote the regeneration of nerve connections following spinal cord injuries.
Work by the team of Dr. Frédéric Charron , director of the Molecular Biology of Neuronal Development Research Unit at the Montreal Clinical Research Institute and professor-researcher in the Department of Medicine at the University of Montreal, recently published in the Journal of Neuroscience, highlights the fundamental role of a family of proteins, β-arrestins, in the development of the nervous system at the embryonic stage.
This breakthrough was made possible thanks to the work carried out by doctoral student Rachelle Sauvé, in collaboration with Steves Morin, then a research assistant, and Dr. Patricia Yam in Frédéric Charron's laboratory.
"This new understanding opens up our perspectives to better explore the mechanisms that can lead to the regeneration of nerve connections following spinal cord injuries," explains the researcher. "And the more we dismantle these mechanisms, the more we will be able to act to correct the after-effects resulting from these injuries."
The role of proteins in axon guidance
During embryonic development, neurons extend their axons, a long cellular cable that allows them to connect specific areas of the body, thus establishing nerve connections.
The set of processes that govern the elongation of the axon and guide its navigation is called "axon guidance". Among other things, axon guidance connects each neuron to its specific target. It is therefore crucial for the proper development of the nervous system. Various so-called guidance molecules, such as Sonic hedgehog, direct axons to their targets like road signs directing axons to their destination. However, the perception of these guidance molecules by axons requires complex molecular machinery that has not yet revealed all its mysteries.
Frédéric Charron's team has demonstrated, for the first time, that β-arrestin proteins serve as adaptors between Smo and SFK proteins, two essential components of axon guidance. Like an electronic adapter without which it would be impossible to plug your phone into a power outlet, β-arrestin proteins allow Smo and SFK proteins to interact with each other. Thus, β-arrestins are essential for axon guidance.
About the study
The article “ β-arrestins are scaffolding proteins required for Shh-mediated axon guidance ,” by Rachelle Sauvé and colleagues, was published in the Journal of Neuroscience on June 17, 2024.
This study was made possible by the support of the Canadian Institutes of Health Research, the Canada Foundation for Innovation, the Fonds de recherche du Québec – secteur Santé and the Canada Research Chairs Program. (Newswise/AD)