Toxins force the construction of “roads to nowhere”

This image shows the effects of the VopF toxin, shown in green in the left cell, on actin filaments, shown in magenta in both cells. Credits: Elena Kudryashova

Toxins released by a type of bacteria that cause diarrheal disease hijack cellular processes and force important proteins to assemble into ‘roads to nowhere’, redirecting proteins away from other tasks essential for cells to function properly, according to a new study.

The proteins affected are known as actins, which are very abundant and have multiple roles, including helping each cell unite its contents, maintain its shape, divide and migrate. Actins assemble into threadlike filaments to perform certain jobs inside cells.

The researchers discovered that two toxins produced by the vibrio This kind of bacteria causes actins to start clumping together in these filaments – which could be thought of as cellular highways on which cargo is delivered – to the wrong place inside cells and in the wrong direction.

“Growth in the wrong direction is a completely new function that was not known before and was not thought to be possible for actin filaments inside the cell,” said lead author Dmitri. Kudryashov, associate professor of chemistry and biochemistry at Ohio State University. “Much of the actin in the cell is consumed in the formation of ‘highways’ where it is not needed, so cellular resources are wasted and cannot be used to meet the basic needs of the cell. “

The research is published today (18 November 2022) in the journal Scientists progress.

These disruptive toxins are called VopF and VopL and are produced by two strains of vibrio bacteria living in seawater: V.cholerae and V. parahaemolyticusboth of which can contaminate oysters and other shellfish which, when eaten raw, make people sick.

In this study, the research team focused on describing unexpected cellular activities rather than other implications, such as the relationship between hijacking and bacterial infection.

“We are looking at interference at the molecular level – we haven’t focused here on how this cellular function might affect humans,” said first author and co-correspondent Elena Kudryashova, researcher in chemistry and biochemistry at the Ohio State.

“From a practical perspective, it tells us more about these pathogens, and knowing your enemy helps you fight your enemy,” she said. “But finding something that we didn’t know was possible – that actin behaves this way inside the cell – raises new questions about whether this function might actually be necessary or might just happen. produce in another way.”

Until now, actins were known to assemble each filament in a unique way, starting from what is called its pointed end and directed towards what is called the barbed end of the structure. Because they are limited in number, actins disassemble as needed from the pointed end and are recycled to maintain directional activity towards the barbed end, then these actin filaments perform functions, such as migration , contraction or cell division, as dictated by what the cell commands.

However, when VopF and VopL toxins enter a cell, they attract actin molecules to create a new filament and cause the filaments to assemble there, causing them to lengthen in the direction of the pointed end – a reversal of their habit. direction of elongation.

“The toxins start creating these actin filament highways in the wrong place, building something that’s useless to the cell, and the cell doesn’t know how to deal with it,” Kudryashov said.

This actin interference has been observed using live cell imaging containing individual toxin molecules. While they don’t yet know the full consequences of this hijacking activity, the researchers said the results could include seepage of nutrients through damaged intestinal walls, providing food for infectious bacteria waiting inside. ‘outside.

“Killing cells isn’t always necessary – disrupting cell barrier function can also benefit pathogens,” Kudryashova said.

And that’s why scientists want to know more – whether other molecules can force actins to assemble ‘roads to nowhere’ and whether this strange filament formation might even be a beneficial mechanism under different circumstances.

“It’s entirely possible that our own cells do this on some occasion, but we don’t know because actin has so many functions and not all of them are well understood yet,” Kudryashov said.

The Ohio State team collaborated with co-authors Ankita, Heidi Ulrichs and Shashank Shekhar of Emory University.

More information:
Elena Kudryashova et al, Processive pointed-end elongation of actin filaments by Vibrio VopF and VopL effectors, Scientists progress (2022). DOI: 10.1126/sciadv.adc9239

Provided by Ohio State University

Quote: Toxins force construction of ‘roads to nowhere’ (November 18, 2022) Retrieved November 19, 2022 from

This document is subject to copyright. Except for fair use for purposes of private study or research, no part may be reproduced without written permission. The content is provided for information only.

Leave a Reply

Your email address will not be published. Required fields are marked *