The Johns Hopkins and Florida State teams discovered Kibra by studying ovarian cells from adult flies and by using a gene-controlling technique called RNA interference (RNAi) to systematically turn off each of the approximately 14,000 genes in the fly genome, one at a time, in cultured fly cells. They then analyzed the function of Kibra in the developing fly larvae. Each of the specialized discs that develop into a fly's eyes starts out with approximately 30 to 40 cells and then grows by about a thousand-fold in the larval stage before stopping, making larvae the ideal place to catch the right-sizing process in action, Pan says. These studies told them that the Hippo pathway was not active in the absence Kibra.

Further studies on human cells measured the activity of the Hippo pathway while manipulating human Kibra and showed that like its fruit fly counterpart, human Kibra acts as a tumor suppressor protein that regulates Hippo signaling.

"The discovery of Kibra moves us an important step closer to identifying the initial signal that triggers Hippo's activation," Pan says. "We're making progress along the Hippo pathway, heading toward the cell surface, and believe we will find that elusive signal en route."

The name Kibra, a shortened combination of the words kidney and brain, is based on earlier evidence that Kibra is prominently expressed in those two organs. Kibra's role in memory performance in humans has already garnered interest.

Source: Johns Hopkins Medical Institutions