Mechanisms of cargo transport by microtubule motors

Microtubule-based motors are critical for cell organization and function. In neuronal axons, inbound (dynein) and outbound (kinesin) motors are coordinated to direct the correct delivery of organelles, RNAs and proteins, and can be hijacked by pathogens such as herpes viruses. These cargos recruit motors by different, but incompletely defined, networks of interactions involving several families of adaptor proteins. Surprisingly, both cargos and individual adaptors can simultaneously recruit dynein and kinesins. This leads to the question of how direction, distance of travel and other behaviours are controlled to achieve the desired cargo distribution. Our work aims to 1) identify the network of connections linking motors to specific cargos and 2) understand how the connections control motor activity. We will develop crosslinking mass spectrometry methods to identify motor:cargo interactions in neurons. This will complement detailed mechanistic studies using live-cell imaging, cryo-EM and reconstitution approaches. Our discovery-based research will uncover the molecular principles underlying cargo delivery in cells.