UCSD Researchers Identify Protein With Dual Role In Regulation Of Cellular Processes

This is the first scientific evidence that links an important regulatory protein to both cell signaling (a complex cellular communication process) and membrane trafficking (the movement of substances through the cell’s outer membrane to targeted areas within the cell).

According to senior author Marilyn Farquhar, Ph.D., chair of UCSD’s Department of Cellular and Molecular Medicine, the findings are important to the scientific community because they link previously unconnected areas and offer new avenues of disease research.

“For example,” she added, “these findings offer potential targets for the development of new drugs to help people with heart failure, hormone imbalances and cancer, which are all linked to flaws in cell signaling or trafficking.”

In its cell-signaling role, RGS-PX1 regulates a molecular on-off switch called a G protein alpha (Ga) subunit, which is important for cellular processes that affect a variety of conditions such as normal heart beat, hormone secretion, and kidney function. When RGS-PX1is present, the Ga subunit activity is turned off.

Bin Zheng, M.S., a graduate student in UCSD’s Molecular Pathology Graduate Program and the study’s first author, noted that RGS-PX1 also modulates trafficking within the cell, specifically the movement of cellular components called growth factor receptors, which influence cell growth and division.

In normal activity, when cell growth is completed, growth factor receptors cease their activity. RGS-PX1 delays the natural degradation of growth factor receptors and, instead, allows cells to continue to proliferate, such as in the growth of cancerous tumors.

“Now we need more studies to determine other molecules involved and how RGS-PX1 is activated in its regulation of cell signaling and growth factor trafficking,” Zheng said.

Farquhar likened it to the electrical circuits in a house where the current comes in one main circuit, then branches out to different rooms.

“Signaling circuits are like that,” she said. “Right now we’re in the family room, where we discovered the protein. We’re now trying to work our way back to the entry point where this is controlled, to better understand how and why RGS-PX1 gets activated.”

Found in yeast, plants and mammals, there are at least 20 RGS proteins that were first described by researchers about six years ago. The Farquhar team found one of the first RGS proteins and has continued their studies since then. About two years ago, Zheng found the RGS-PX1 protein while searching many of the new protein and DNA sequence databases, then determined its function with laboratory studies of various animal cells. The team named the protein RGS-PX1 to include both its roles: RGS for the G protein signaling function, and PX to signify its physical structure related to trafficking.

Additional authors of the study were Gordon Gill, M.D., professor and interim dean for scientific affairs, UCSD School of Medicine; Paul A. Insel, M.D., professor, and Rennolds S. Ostrom, Ph.D., post doctoral fellow, UCSD Department of Pharmacology; Christine Lavoie, Ph.D., assistant project pharmacologist, UCSD Department of Cellular and Molecular Medicine; and Yong-Chao Ma, Ph.D., post doctoral fellow and Xin-Yun Huang, Ph.D., professor, Department of Physiology, Weill Medical College of Cornell University.

The research was funded by the National Institutes of Health.