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

Abstract

Molecular 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 5HT(1A) receptor (5HT(1A)R) transport. The cell-surface expression level of the 5HT(1A)R 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 5HT(1A)R are the interface between the motor and cargo vesicles. A minimotor consisting of the motor and FHA domains is able to transport 5HT(1A)R-carrying organelles in invitro reconstitution assays. Collectively, our results suggest a role for this molecular motor in anxiety control.