In the brain, broken down 'motors' cause anxiety

The study in mice focuses on one motor in particular, known as KIF13A, which, according to the new evidence, is responsible for ferrying serotonin receptors. Without proper transportation, those receptors fail to reach the surface of neurons and, as a result, animals show signs of heightened anxiety.

In addition to their implications for understanding anxiety, the findings also suggest that defective molecular motors may be a more common and underappreciated cause of disease.

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This video (S3 in the paper) shows the transport defect of the serotonin receptor in a KIF13A knock out neuron compared with a wild type neuron. Credit: Cell Reports, Zhou et al.

"Most proteins are transported in vesicles or as protein complexes by molecular motors," said Nobutaka Hirokawa of the University of Tokyo. "As shown in this study, defective motors could cause many diseases."

Scientists know that serotonin and serotonin receptors are involved in anxiety, aggression, and mood. But not much is known about how those players get around within cells. When Hirokawa's team discovered KIF13A at high levels in the brain, they wondered what it did.

The researchers discovered that mice lacking KIF13A show greater anxiety in both open-field and maze tests and suggest that this anxious behavior may stem from an underlying loss of serotonin receptor transport, which leads to a lower level of expression of those receptors in critical parts of the brain.

"Collectively, our results suggest a role for this molecular motor in anxiety control," the researchers wrote. Hirokawa says the search should now be on for anti-anxiety drug candidates aimed at restoring the brain's serotonin receptor transport service.

More information: Cell Reports, Zhou et al.: "A Molecular Motor, KIF13A, Controls Anxiety by Transporting the Serotonin type 1a Receptor." dx.doi.org/10.1016… .2013.01.014

Journal reference: Cell Reports

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