Augmin And g-Tubulin Promote Axonal Microtubule Formation

A new molecular mechanism that plays a key role in forming and maintaining axons has been described by scientists at the Institute for Research in Biomedicine, headed by Jens Lüders.

The finding could help research into regenerative medicine and potentially also help understand neurodegenerative diseases such as Alzheimer’s.

Neurons send a constant flow of substances and signals along axons, which are neuronal extensions that in humans can reach lengths of up to one meter. Inside axons is a dense network of microtubules, thin filaments that drive the growth of the axon, and at the same time serve as transport channels for cellular components.

“Neurons are cells that are especially dependent on microtubules, not only to transport internal cellular components, but also to facilitate communication between themselves. Curiously, until now we haven’t known how these microtubules are formed and organized,” says Jens Lüders.

Repurposing A Molecular Complex For Axonal Microtubule Formation

Studying hippocampi in mice, the researchers observed that differentiated neurons – those that had lost the ability to divide – use a molecular complex that until now has only been known to play a role in cell division to generate new microtubules within their axons.

First author Carlos Sánchez-Huertas, postdoctoral researcher in Lüders group at IRB Barcelona and currently at the Centre de Recherche de Biologie Cellulaire (CNRS) in Montpellier, comments:

“This complex plays a determining role in the formation and maintenance of the neuronal axon, one of the most enigmatic cellular structures. I believe scientists will discover more cases of cell division proteins being re-used by post-mitotic cells for other molecular activities.”

The scientists propose that in neurons, the complexes formed by Augmin and g-Tubulin (γTuRC) promote the formation of new microtubules along already existent ones. The new microtubule ‘inherits’ the same orientation as the previous one, leading to the formation of bundles of microtubules with the same polarity, which is a fundamental characteristic of axons.

Understanding how microtubules form and how they are organized in a complex and structured network within neurons is key to making advances in neuroscience. These processes can offer insight into the regeneration of axons, a step that is necessary for medullar lesion repair, but which still remains be achieved.

The study also may provide insight into neurodegenerative diseases, such as Alzheimer’s, in which the microtubule network is damaged.

The work was funded by the Ministry of Economy and Competitiveness, and FEDER, and included a collaboration with scientists from the University of Barcelona.

Carlos Sánchez-Huertas, Francisco Freixo, Ricardo Viais, Cristina Lacasa, Eduardo Soriano, Jens Lüders
Non-centrosomal nucleation mediated by augmin organizes microtubules in post-mitotic neurons and controls axonal microtubule polarity
Nature Communications, 2016; 7: 12187 DOI: 10.1038/ncomms12187

Image: Microscopy image of a culture mouse neuron showing the microtubule network in green and red depending on chemical modifications. The axon, in bright green, is the neuronal extension that has the greatest number of modified microtubules. Credit: Carlos Sánchez-Huertas, IRB Barcelona