Scientists at the Washington University School of Medicine in St. Louis have discovered a new link between two key proteins that regulate the placement of cell parts.
Special placement of the various parts of a cell — a phenomenon scientists call cellular polarity — is essential for many life-sustaining functions. During development, moving parts to a particular region of a cell allows that region to become specialized when the cell divides. In a mature organism, cellular polarity allows a single cell to develop sides with multiple functions. For example, a cell that is part of an organ will develop different specialized properties on its sides that abut other organ cells (known to scientists as the basolateral surfaces) than on the sides of the cell that face the organ’s exterior or cavities (known as the apical surfaces).
In a paper published in Current Biology, researchers demonstrate that an important polarity-regulating protein called Par-1 can be shut down when another protein called atypical PKC, also shown to be a major player in polarity, attaches a regulatory molecule to Par-1.
Cancer cells frequently lose their polarity, and disruption of polarity-regulating proteins, which occurs in the inherited disorder Peutz-Jeghers syndrome, has been linked to dramatically increased cancer risk.
“By the age of 43, the vast majority of these patients develop malignant tumors, mostly of the gut, but in other places too,” explains Helen Piwnica-Worms, Ph.D., professor of cell biology and physiology and of medicine at Washington University School of Medicine. “They develop polyps in the epithelial cells of the gut, or the cells that line the cavity of the gut, and over time these develop into malignant tumors.”
Piwnica-Worms notes that her lab already has identified another site on Par-1 where a regulatory molecule can be attached to the protein. She plans to investigate its effects on Par-1’s activity and says she is certain that they’ve just begun to glimpse the complex web of regulatory connections that exists between several proteins that can influence cellular polarity.
“Over the last couple of years, we’ve just started to be able to take these molecules and study the pathways they regulate in detail,” says Piwnica-Worms, who also is a Howard Hughes Medical Institute investigator. “They are essential for proper function in a wide variety of organs and systems, so fully understanding how they are regulated is eventually going to be very important to our ability to treat a range of different disorders.”
Hurov JB, Watkins JL, Piwnica-Worms H. Atypical PKC phosphorylates PAR-1 kinases to regulate localization and activity, Current Biology, April 20, 2004.
Funding from the Howard Hughes Medical Institute.
The full-time and volunteer faculty of Washington University School of Medicine are the physicians and surgeons of Barnes-Jewish and St. Louis Children’s hospitals. The School of Medicine is one of the leading medical research, teaching and patient care institutions in the nation, currently ranked second in the nation by U.S. News & World Report. Through its affiliations with Barnes-Jewish and St. Louis Children’s hospitals, the School of Medicine is linked to BJC HealthCare.