Cilia in the brain may be busier than previously thought

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Nerve cells in the brain make elaborate connections and exchange lightning-quick messages that captivate scientists. But these cells also sport simpler, hairlike protrusions called cilia. Long overlooked, the little stubs may actually have big jobs in the brain.

Researchers are turning up roles for nerve cell cilia in a variety of brain functions. In a region of the brain linked to appetite, for example, cilia appear to play a role in preventing obesity, researchers report January 8 in three studies in Nature Genetics. Cilia perched on nerve cells may also contribute to brain development, nerve cell communication and possibly even learning and memory, other research suggests.

“Perhaps every neuron in the brain possesses cilia, and most neuroscientists don’t know they’re there,” says Kirk Mykytyn, a cell biologist at Ohio State University College of Medicine in Columbus. “There’s a big disconnect there.”

Most cells in the body — including those in the brain — possess what’s called a primary cilium, made up of lipid molecules and proteins. The functions these appendages perform in parts of the body are starting to come into focus (SN: 11/3/12, p. 16). Cilia in the nose, for example, detect smell molecules, and cilia on rod and cone cells in the eye help with vision. But cilia in the brain are more mysterious.

The new research offers some clarity. In one study, molecular geneticist Christian Vaisse of the University of California, San Francisco, and colleagues studied mutations in a protein called MC4R that are known to cause severe obesity in people. Experiments on mice showed that MC4R normally resides within the cilia on appetite-controlling nerve cells. But several of these mutations prevented MC4R from reaching those cells’ cilia from elsewhere in the cells, experiments on cells in dishes showed. And one of these mutations prevented MC4R from reaching nerve cell cilia in the brains of mice.

When the researchers interfered with ADCY3, a protein in the cilia that helps MC4R regulate appetite, the resulting mice became obese. Those results suggest that MC4R must reach the cilia in order to interact with ADCY3 and work properly. In the other two papers, scientists link the ADCY3 gene to obesity in people, providing more evidence that cilia are involved in obesity.

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