St. Jude Children’s Research Hospital molecular biologists have identified an enzyme that activates and “supercharges” cellular machinery that controls how cells become specialized cells in the body.
Malfunction of that machinery, dubbed the Sonic Hedgehog pathway, causes a variety of developmental disorders and cancers, including childhood medulloblastoma and basal cell carcinoma. Researchers believe their basic discovery opens a new research pathway that could lead to drugs to treat such disorders.
Led by Stacey Ogden, Ph.D., an associate member of the St. Jude Department of Cell and Molecular Biology, the research was published June 6 in the journal Cell Reports.
The scientific puzzle the researchers sought to understand was how a major activator of the Sonic Hedgehog pathway, called Smoothened, manages to make its way into an antenna-like cell structure called a “primary cilium,” where it communicates with its downstream signaling partners.
Every cell in the body sprouts a primary cilium, which harbors a whole factory of cellular machinery that the cell uses to translate external stimuli into cell responses. Such stimuli include mechanical movement and chemical signals such as hormones. Normally, Smoothened is barred from the primary cilium, keeping the Sonic Hedgehog pathway safely controlled.
In their experiments with cell cultures, the researchers discovered that an enzyme called Phospholipase A2 triggers a mechanism that opens the way for Smoothened movement into the cilium. What’s more, the phospholipase triggers an amplification that…