Putting the brakes on a myosin motor

Abstract

Insulin-stimulated trafficking of GLUT4 requires the myosin motor Myo1C and signaling adaptor 14-3-3β. Originally, it was thought that 14-3-3β promotes GLUT4 transport by binding the Myo1C lever arm and activating the Myo1C motor. New work by Ji and Ostap using in vitro assays reveals that 14-3-3β binding actually inhibits Myo1C motility, prompting reconsideration of the functional relationship between 14-3-3β and Myo1C and the regulatory potential of atypical light chains.

Figure 1.

14-3-3β competes with CaM for Myo1C binding to the lever arm. A, three apo-CaM molecules bind the Myo1C lever arm (LA) when intracellular calcium is low, interfering with 14-3-3β association with Myo1C. B, insulin stimulation causes an increase in intracellular calcium, dissociating CaM from the first IQ domain (IQ1), allowing the 14-3-3β dimer to bind. C, 14-3-3β could link Myo1C to GLUT4-containing vesicles and membrane fusion machinery to the membrane, allowing the motor to tether the vesicle to the cortical actin network. D, high calcium causes CaM dissociation from the Myo1C lever arm, exposing hydrophobic patches, which can cause Myo1C aggregation. 14-3-3β binding the lever arm may prevent Myo1C aggregation when calcium is high.