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Transport Breakdown

Deficiencies in a cellular motor that carries a serotonin receptor are associated with anxiety in mice.

By | July 1, 2013

EDITOR'S CHOICE IN BIOCHEMISTRY

KEEPING THE MOTORS TUNED: Anxiety may be caused by defects in motor proteins (such as the kinesin protein depicted here) that shuttle vesicles containing serotonin receptors around neurons.© GUNILLA ELAM/SCIENCE SOURCE IMAGES

The paper
R. Zhou et al., “A molecular motor, KIF13A, controls anxiety by transporting the serotonin type 1a receptor,” Cell Reports, 3:509-19, 2013.

The finding
Dysfunctions in the neurotransmitter serotonin and its receptors have long been associated with anxiety. University of Tokyo cell biologist Nobutaka Hirokawa and colleagues have found that the kinesin motor KIF13A transports serotonin type 1a receptors to the cell membrane, and that defects in KIF13A result in anxiety-related behavior in mice.

The search
Hirokawa previously found that KIF molecular motors are involved in diverse processes, including nerve development and higher brain functions such as learning and memory. The function of KIF13A, however, was a mystery. While performing behavioral screens on mice lacking KIF13A, Hirokawa’s team noticed many hallmarks of anxiety. Also, hippocampal cells from the mutants contained markedly fewer serotonin type 1a receptors.

The mechanism
To watch KIF13A in action, the researchers tagged serotonin type 1a receptors with green fluorescent protein. In cultures with normal KIF13A expression, the receptors successfully traveled to the plasma membrane, while in cultures lacking KIF13A, the receptors gathered near the nucleus. The paper “provides a quite interesting model of why serotonin 1a receptors are expressed to a lower extent in people with anxiety disorders,” says Alexander Neumeister, a translational neuroscientist at New York University’s Langone Medical Center.

The application
Considering what is known about serotonergic system deficits, Hirokawa says that he is convinced that problems with KIF13A play a role in anxiety in humans. “If we can generate the chemicals to activate KIF13A motor protein activity, then this can be used as a drug to treat the problem of anxiety,” he adds.

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