A Molecular Motor, KIF13A, Controls Anxiety by Transporting the Serotonin Type 1A Receptor

SummaryMolecular motors are fundamental to neuronal morphogenesis and function. However, the extent to which molecular motors are involved in higher brain functions remains largely unknown. In this study, we show that mice deficient in the kinesin family motor protein KIF13A (Kif13a−/− mice) exhibit elevated anxiety-related behavioral phenotypes, probably because of a reduction in 5HT1A receptor (5HT1AR) transport. The cell-surface expression level of the 5HT1AR was reduced in KIF13A-knockdown neuroblastoma cells and Kif13a−/− hippocampal neurons. Biochemical analysis showed that the forkhead-associated (FHA) domain of KIF13A and an intracellular loop of the 5HT1AR are the interface between the motor and cargo vesicles. A minimotor consisting of the motor and FHA domains is able to transport 5HT1AR-carrying organelles in in vitro reconstitution assays. Collectively, our results suggest a role for this molecular motor in anxiety control.

Graphical AbstractFigure optionsDownload as PowerPoint slideHighlights
► Kif13a−/− mice show elevated-anxiety-like behavioral defects
► 5HT1A receptors are not properly transported in Kif13a−/− neurons
► The forkhead-associated domain of KIF13A associates directly with 5HT1A receptors
► KIF13A can translocate 5HT1A receptors in vivo and in vitro