Cell complexity: talking through microtubules (Introduction)

by David Turell , Tuesday, May 08, 2018, 00:28 (2393 days ago) @ David Turell

This is another way of communicating:

https://www.scientificamerican.com/article/cells-talk-and-help-one-another-via-tiny-tub...

"Finally, after delving into the literature, Lou realized that the lines matched what Hans-Hermann Gerdes’ group at the University of Heidelberg had described as “nanotubular highways” or “tunneling nanotubes” (TNTs) in a 2004 paper in Science.

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"In the last few years, the number of researchers working on TNTs and figuring out what they do has risen steeply. Research teams have discovered that TNTs transfer all kinds of cargo beyond microRNAs, including messenger RNAs, proteins, viruses and even whole organelles, such as lysosomes and mitochondria.

"These fragile structures are appearing not only in the context of conditions such as cancer, AIDS and neurodegenerative diseases, but also in normal embryonic development. Healthy adult cells don’t usually make TNTs, but stressed or ailing cells appear to induce them by sending out signals to call for help. It’s unclear, though, how healthy cells sense that their neighbors need help or how they physiologically “know” what specific cargo to send.

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"With microscopy techniques, the group examined the structures further and determined that they are open channels through which organelles and membrane vesicles move from one cell to another. At that point it became clear that the membrane tubes were “a completely new mechanism of cell-cell communication,” Rustom explained. It was not so easy, however, to convince others—some researchers suspected that these TNTs were experimental artifacts, not naturally occurring structures. It took the group four or five years to publish their paper because of the strong skepticism with which the findings were met, he said.

"Confirming that TNTs are indeed an avenue for intercellular communication has continued to be a major challenge. Cells have other options for exchanging molecules, most notably the structures called gap junctions and exosomes.

"If TNTs are akin to skywalks, the enclosed footbridges that connect separate buildings, then gap junctions—gated pores that pass through the membranes of neighboring cells—are like doorways between adjacent rooms. Exosomes, small vesicles shed by cells, were long thought to be cellular trash bags carrying debris, but scientists now recognize them as vehicles for carrying microRNAs and other signaling molecules between cells, sometimes over long distances. The challenge in identifying the role of TNTs is that it’s tricky to inhibit any one of these communication channels without interfering with the others.

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"What complicates matters is that TNTs appear in a wide variety of cell types and are morphologically diverse, showing up in a wide range of sizes. In some cases they are large enough to be considered microtubes rather than nanotubes, and some researchers believe that the smaller TNTs are functionally different from microtubes. Efforts are ongoing to characterize the different subtypes of nano- and microtubes.

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"Before his eyes, the mRNA molecules migrated through TNTs bridging the different cells. “I could actually see the mRNA is found in the membrane nanotubes, and that if I inhibit membrane nanotube formation … I abolish RNA transfer,” he said.

"To understand whether or not the cells actively regulate these transfers, Haimovich challenged them with heat shock and oxidative stress. If changes in the environmental conditions changed the rate of RNA transfer, that “would suggest that this is a biologically regulated mechanism, not just diffusion of RNA by chance,” he explained. He found that oxidative stress did induce an increase in the rate of transfer, while heat shock induced a decrease. Moreover, this effect was seen if stress was inflicted on acceptor cells but not if it was also inflicted on donor cells prior to co-culture, Haimovich clarified by email. “This suggests that acceptor cells send signals to the donor cells ‘requesting’ mRNA from their neighbors,” he said."

Comment: They certainly do communicate, if mRNA can be see travelling down the tubules. This adds to the complexity of intercellular communication. Not by chance.