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Regulation of cytoplasmic dynein-1 by Lis1 - 5 July 2022

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Speaker Professor Andres Leschziner, Department of Cellular and Molecular Medicine & Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego

Title Regulation of cytoplasmic dynein-1 by Lis1

Host Mark Sanderson


Abstract Cytoplasmic dynein-1 (“dynein”) is a molecular motor that drives nearly all minus-end-directed microtubule-based transport in human cells. Dynein’s functions range from retrograde axonal transport to mitotic spindle assembly. While dynein by itself exists in an autoinhibited conformation, cargo-transporting dynein is part of a ~4 MDa complex consisting of one or two dynein dimers, the dynactin complex and an 'activating adaptor'. We are interested in understanding how dynein is activated and assembled into these transport complexes, about which little is known. A key player in these processes is another dynein regulator: Lis1. Lis1 is the product of the lissencephaly 1 gene, LIS1, which is mutated in patients with the neurodevelopmental disease lissencephaly. The Lis1 protein, a small 90 kDa dimer, is conserved from fungi to mammals, and is the only dynein regulator known to bind directly to dynein’s motor domain, where it alters dynein’s mechanochemistry. I will discuss our current structural and mechanistic understanding of Lis1’s role in the formation of fully active dynein complexes.

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