Gene Influencing Rheumatic Diseases Regulates Cell Movement

Researchers from Karolinska Institutet, collaborating with colleagues from Linköping University, have identified the function of the gene DIORA1 (FAM167A), which has been previously associated with autoimmune rheumatic conditions such as rheumatoid arthritis, systemic lupus erythematosus, and Sjögren's syndrome. Prior to this discovery, the precise role of DIORA1 within the body remained unclear.

The team uncovered that DIORA1 plays a crucial role in controlling cell motility by interacting with a family of proteins called MRCK kinases. These kinases are vital for determining the cell's skeleton and its capacity to move. Using advanced cellular techniques, they demonstrated that DIORA1 binds directly to MRCK kinases, affecting their activity and consequently influencing the cell's structural dynamics.

To explore this interaction further, scientists employed proximity proteomics to identify proteins near DIORA1 within human cells. They confirmed the binding between DIORA1 and MRCK kinases and mapped out the interaction pathways. When DIORA1 expression was reduced in human cells via CRISPR gene editing, researchers observed significant changes in gene activity and protein modifications linked to cell movement. Notably, these changes resulted in cells displaying an increased ability to invade surrounding tissues.

Understanding the cellular functions of genes like DIORA1 could illuminate the mechanisms underlying rheumatic diseases and open pathways for novel treatments in the future. As Professor Marie Wahren-Herlenius explains, "We now understand that DIORA1 regulates cell mobility by interacting with MRCK kinases, providing insight into the cellular mechanisms linked to autoimmune conditions."

Future research aims to examine how DIORA1 influences the immune system at the organismal level, including studies using animal models that lack this gene, to better understand its role in immune regulation and disease development.

The findings of this research are published in the journal Proceedings of the National Academy of Sciences. These insights mark an important step in understanding the genetic factors that contribute to rheumatic diseases and may lead to targeted therapies that modify cell movement and immune responses.