GSK-3 regulates transport of kinesin-1 driven cargos in vivo

The Glycogen Synthase Kinase 3 (GSK-3) has been linked to many aspects of the development of Alzheimer's disease and was proposed to play a role in the transport of the Amyloid Precursor Protein (APP) by kinesin-1 motors. Using Drosophila embryos and larvae with altered GSK-3 expression, we characterize motor transport of cargos including APP and lipid droplets using DIC microscopy, high-resolution video tracking, fluorescence, and in vivo stall force measurements with optical tweezers. By comparing cargo velocities and run lengths we find that GSK-3 is a required negative regulator of in vivo transport. Stall force measurements on lipid droplets reveal that enhanced transport under conditions of reduced GSK-3 is a result of a larger number of active motors hauling the cargo. Our findings have implications on the use of GSK-3 inhibitors in treatment of Alzheimer's disease.