They demonstrated that the agouti protein prevented the melanocortin-1 receptor in melanocytes (pigment cells) in the skin from switching on production of black-brown pigment, and instead shifted the pigment to yellow-red hues.

The second agouti gene encodes agouti-related protein (AgRP), which blocks a melanocortin receptor in the brain. It prevents the melanocortin-4 receptor from inhibiting food intake, and thus stimulates eating.

In the current paper, Cone's group reports that the newly discovered protein, AgRP2, regulates expression of the prohormone genes pmch and pmchl, precursors to melanin-concentrating hormone, which has a pigment-lightening effect.

"Together, the versatile agouti proteins and melanocortin receptors are responsible for regulation of body weight, the banded patterns of mammalian coats, and even red hair in most people," Cone said. The current work shows that agouti proteins are also involved in the camouflage mechanisms used in thousands of fish species.

Cone, who came to Vanderbilt in 2008, has spent most of his career studying how the melanocortin receptors in the brain regulate body weight. He and his colleagues have published more than three dozen papers elucidating elements of this complex signaling system.

Source: Vanderbilt University Medical Center