Transport of organelles, RNAs and proteins is essential for the development, health and function of neurons. Defects in the microtubule motors that drive the transport is linked to neurodegenerative and developmental diseases and the transport process is frequently hijacked by viruses. Yet how motors are linked to cargos and how they are coordinated to ensure delivery to the correct destination is poorly understood.
This PhD project will address these questions by combining cellular imaging, in vitro reconstitutions and cryo-electron microscopy (cryo-EM) or tomography (cryo-ET). We will use an inducible neuron system (iNeurons), established in the lab, to identify the adaptors that link dynein and kinesin motors to specific cargos. This will guide in vitro and structural studies to address how motor activity is controlled and how the unique combinations of components present on a cargo determine the direction it moves.
References
Foster HE, Ventura Santos C, Carter AP (2022) A cryo-ET survey of microtubules and intracellular compartments in mammalian axons. J Cell Biol. 221:e202103154.
Chaaban S and Carter AP‡ (2022) Structure of dynein-dynactin on microtubules shows tandem recruitment of cargo adaptors. Nature. 611:E8.
Fellows AD, Bruntraeger M, Burgold T, Bassett AR, Carter AP (2023) Dynein and dynactin move long-range but are delivered separately to the axon tip bioRxiv doi: https://doi.org/10.1101/2023.07.03.547521
Singh K, Lau CK, Manigrasso G, Gama JB, Gassmann R, Carter AP (2023) Molecular mechanism of dynein-dynactin activation by JIP3 and LIS1 bioRxiv doi: