This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: Cornell researchers have used artificial intelligence to uncover a previously unknown way cells control how proteins move inside them, a process essential for growth, communication and movement that is often disrupted in cancer. The study, published Sept. 9 in the Journal of Cell Biology, shows that a little-understood protein called Avl9 acts as an "off switch" for another protein, Arf1, which helps direct where materials go inside cells.
Turning Arf1 off at the right time is critical because it regulates cellular transport; otherwise, cells become disorganized, leading to negative effects. The researchers also found that Avl9 is part of a broader group of proteins that may perform the same function, pointing to a previously unrecognized system cells use to keep this process in balance. Led by Chris Fromme, professor of molecular biology and genetics at the College of Agriculture and Life Sciences and a faculty member at the Weill Institute for Cell and Molecular Biology, the team used AlphaFold, an artificial intelligence program that predicts the structures of proteins and how they might interact, to search for previously unknown partners of Arf1.
Instead of traditional lab screening, which can take months, the AI software quickly generated a shortlist of likely protein interactions for experimental testing. "We discovered an unexpected function of a poorly understood protein, which helps us understand how cells control intracellular trafficking," Fromme said. Arf1 acts as a molecular switch that directs the movement of proteins and other cargo to the right places inside the cell.
Because it is involved in many essential processes, scientists expected additional proteins to exist to control its activity. "Arf1 controls the movement of proteins that need to move from the Golgi to several other destinations in the cell," Fromme said. "Arf1 is essential for many cellular behaviors, including secretion, migration and basic internal organization." "Arf1 is so important and involved in so many different cellular pathways, we felt there had to be more to how cells control its activity than what was already known," he said.
The AI analysis pointed to Avl9, which had been linked to secretion and cancer cell movement but whose function was unknown. Laboratory experiments confirmed that Avl9 shuts down Arf1 after it has carried out its role. "The function of Avl9 was the exact opposite of what you would guess based on what was known about its amino acid composition," said Ryan Vignogna, postdoctoral associate at the Weill Institute and first author of the study.
To confirm the finding, the team tested normal and mutated versions of Avl9 in cells. A single amino acid change eliminated its ability to regulate Arf1. In human lung cancer cells, the change reduced the cells' ability to move, linking the protein's molecular role to a behavior important in cancer.
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