Dynein-mediated cargo transport in vivo: A switch controls travel distance

Cytoplasmic dynein is a microtubule-based motor with diverse cellular roles . Here, we use mutations in the dynein heavy chain gene to impair the motor 's function, and employ biophysical measurements to demonstrate that cytopl asmic dynein is responsible for the minus end motion of bidirectionally mov ing lipid droplets in early Drosophila embryos. This analysis yields an est imate for the force that a single cytoplasmic dynein exerts in vivo (1.1 pN ). It also allows us to quantitate dynein-mediated cargo motion in vivo, pr oviding a framework for investigating how dynein's activity is controlled. We identify three distinct travel states whose general features also charac terize plus end motion. These states are preserved in different development al stages. We had previously provided evidence that for each travel directi on, single droplets are moved by multiple motors of the same type (Welte et al., 1998). Droplet travel distances (runs) are much shorter than expected for multiple motors based on in vitro estimates of cytoplasmic dynein proc essivity. Therefore, we propose the existence of a process that ends runs b efore the motors fall off the microtubules, We find that this process acts with a constant probability per unit distance, and is typically coupled to a switch in travel direction. A process with similar properties governs plu s end motion, and its regulation controls the net direction of transport.