A new study published in the prestigious journal Nature Communications reveals the essential role of a specific enzymatic modification of the neuronal cytoskeleton in the formation of neural connections (synapses). The research was significantly contributed to by a team led by Martin Balaštík from the Laboratory of Molecular Neurobiology of IPHYS.
The authors demonstrate that a microtubule modification, known as polyglutamylation, acts as a “tag” marking them for degradation during synaptic remodelling — the process by which redundant synapses are selectively removed during development. Using genetic mouse models, they proved that the level of polyglutamylation precisely regulates both the rate and extent of synapse pruning in the peripheral (neuromuscular junctions) and central nervous systems (hippocampus).
The findings suggest that the regulatory enzymes controlling tubulin polyglutamylation represent an important checkpoint in the development and optimization of neural networks and may also play a role in neurodevelopmental or neurodegenerative disorders.
The study emerged from an international collaboration between M. Balaštík’s team and research groups at the Technical University of Munich, ZMNH Hamburg, and the Institut Curie in Orsay, France.
Reference: Gavoci A., Zhiti A., Rusková M., Magiera M. M., Wang M., Ziegler K. A., Hausrat T. J., Ugwuja A. I., Chakraborty S., Engelhardt S., Kneussel M., Balastik M., Janke C., Misgeld T., Brill M. S.: Polyglutamylation of microtubules drives neuronal remodeling. Nature Communications 16:5384 (2025). IF = 15,7 DOI:10.1038/s41467-025-60855-6
