A recent study from Karolinska Institutet reveals how a gene associated with several rheumatic diseases affects how cells move, providing new insights into disease mechanisms and potential future therapies. The study was recently published in the scientific journal PNAS.
A team of researchers at Karolinska Institutet, together with colleagues from Linköping University, have uncovered the function of a gene called DIORA1 (FAM167A), previously linked to autoimmune rheumatic diseases such as rheumatoid arthritis, systemic lupus and Sjögren's disease. Until now, the role of DIORA1 in the body was unknown.
"We have long known that DIORA1 is linked to autoimmune diseases, without understanding its function. Now we show that the gene regulates the cell's ability to move by interacting with a group of proteins known as MRCK kinases," says Marie Wahren-Herlenius , Professor at the Department of Medicine, Solna , Karolinska Institutet and corresponding author of the article.
These kinases are important for the cell's skeleton and its ability to move. Using advanced techniques, the researchers demonstrated that DIORA1 binds to MRCK kinases and influences their activity, which in turn affects the cell's structure and movement.
To investigate this, the team used a method called proximity proteomics to identify which proteins are close to DIORA1 in the cell. They confirmed the interaction with MRCK kinases and mapped out exactly how the proteins connect. By reducing the expression of DIORA1 in human cells using CRISPR technology, the researchers observed changes in gene activity and protein modifications linked to cell movement, as well as an increased ability of cells to invade their surroundings.
"Understanding how genes like DIORA1 function at the cellular level is important for uncovering the mechanisms behind rheumatic diseases and could help in the development of new treatments in the future," says Marie Wahren-Herlenius.
The next step is to investigate how DIORA1 affects the immune system throughout the body, including studies on mice lacking the gene.
The study is a collaboration between researchers at Karolinska Institutet and Linköping University. The researchers from Linköping University contributed with structural modelling of the proteins. The study was funded by the Swedish Research Council, the Knut and Alice Wallenberg Foundation, the Swedish Rheumatism Association, the Swedish Heart-Lung Foundation, and the King Gustav V 80th Birthday Fund.
See publication for any conflicts of interest.
Publication
"Autoimmunity-associated DIORA1 binds the MRCK family of serine/threonine kinases and controls cell motility", Tilen Tršelič, Nathalie Pelo, Gregoire Martin de Fremont, Vaishnavi S. Iyer, Elina Richardsdotter Andersson, Vijole Ottosson, David Alexander Frei, Elisa Baas, William A. Nyberg, Guðný Ella Thorlacius, Lara Mentlein, Sanjaykumar V. Boddul, Ioana Sandu, Diego Velasquez Pulgarin, Ákos Végvári, Carmen Gerlach, Fredrik Wermeling, Maria Sunnerhagen, Björn Wallner, Alexander Espinosa, Marie Wahren-Herlenius, PNAS, 29 September 2025, doi: 10.1073/pnas.2426917122
