When the structure of tunnel nanotubes (TNT) challenges the very concept of cell

Cells connected by nanotubes. Credit: (c) Institut Pasteur

The cells communicate with each other as humans do. This allows the organs to work synchronously, which in turn allows them to perform a remarkable variety of tasks. One of these means of communication is through tunnel nanotubes (TNT). In an article published in Communications of nature, researchers from the Pasteur Institute led by Chiara Zurzolo used advanced imaging techniques to study the structure of these nanotubes and report that the results challenge the very concept of a cell.

As the name implies, TNTs are small tunnels that connect two or more cells and allow the transport of many types of cargo between them, including ions, viruses and complete organelles. Previous research conducted by the same team found that TNT are involved in the intercellular spread of pathogenic amyloid proteins involved in Alzheimer's and Parkinson's diseases. This led the researchers to propose that they serve as an important route for the spread of neurodegenerative diseases in the brain and, therefore, represent a new therapeutic target to stop the progression of these incurable diseases. TNT also seem to play an important role in cancer resistance to therapy. But since scientists still know very little about TNT and how it relates to or differentiates from other cellular protuberances, such as filopodia, they decided to continue their research to treat these small tubular connections in depth.

The dogma of the cellular units questioned.

Therefore, a better understanding of these small tubular connections is required, since TNT can have tremendous implications for health and disease. Addressing this problem has been very difficult due to the fragile and transient nature of these structures, which do not survive clbadical microscopic techniques. To overcome these obstacles, the researchers combined several state-of-the-art electronic microscopy methods and obtained TNT images at subzero temperatures.

Using this strategy of images, they were able to decipher the structure of the TNT in great detail. Specifically, they show that most of the TNTs, which were previously shown to be unique connections, are, in fact, formed by multiple, smaller, individual tunnel nanotubes (iTNTs). His images also show the existence of thin cables that connect the iTNT, which could serve to increase its mechanical stability. They demonstrate the functionality of the iTNT by showing the transport of organelles using time-lapse images. Finally, the researchers used a type of microscopy known as FIB-SEM to produce 3D images with sufficient resolution to clearly identify that TNTs are open at both ends, and thus create continuity between two cells. "This discovery challenges the dogma of cells as individual units, showing that cells can open up to neighboring cells and exchange materials without a membrane barrier," explains Chiara Zurzolo.

A step of news in the decoding of cell-to-cell communication.

By applying an imaging workflow that improves and avoids the previous limitations of the existing tools used to study the anatomy of TNT, researchers have provided the first structural description of TNT. It is important to note that they show that these are new cellular organelles with a defined structure, very different from the known cellular protuberances. "The description of the structure allows the understanding of the mechanisms involved in its formation and provides a better understanding of its function in the transfer of material directly between the cytosol of two connected cells," says Zurzolo. In addition, this strategy, which preserves these delicate structures, will be useful to study the role played by TNT in other physiological and pathological conditions.

This work is an essential step towards the understanding of cell-to-cell communication through TNT and lays the groundwork for the investigation of its physiological functions and its role in the spread of pathogens, including viruses, bacteria and misfolded proteins.

Explore further:
Tunnel nanotubes between neurons allow the spread of Parkinson's disease through lysosomes

More information:
Anna Sartori-Rupp et al, correlative cryoelectron microscopy reveals the structure of TNT in neuronal cells, Communications of nature (2019). DOI: 10.1038 / s41467-018-08178-7

Journal reference:
Communications of nature

Provided by:
Pasteur Institute

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