Microtubule-Based Motors, Organelle
Transport.
The focus of work in our lab is
microtubule-based intracellular organelle transport, the process
responsible for such diverse cell biological functions as
membrane trafficking and mitosis. We study the microtubule motor
enzyme cytoplasmic dynein and its activator, dynactin. Both are
large, multiprotein complexes of several different subunits.
Dynactin is believed to serve as a linker between dynein and its
cargo and, as such, is required for dynein to function normally in
vivo and in vitro. We are currently investigating
several issues central to dynactin structure and function. By
disrupting dynactin function in vivo we can explore how dynein-based motility contributes to endomembrane dynamics,
mitotic spindle assembly and chromosome movement. In vitro
assays for dynein/dynactin-based vesicle motility and spindle
assembly allow us to identify other important molecules such as
receptors and regulatory factors. These studies are being
performed in different model systems such as fibroblasts,
neurons, polarized epithelia and phagocytic cells, each of which
emphasizes a different type of dynein-based motility. We are
presently working to reconstitute dynein and dynactin from their
isolated subunits to further our understanding of how the
structure of each molecule contributes to its function, both in
vivo and in vitro.