The Human Cytoplasmic Dynein Interactome Reveals Novel Activators of Motility

William B. Redwine, Morgan E. DeSantis, Ian Hollyer, Zaw Min Htet, Phuoc Tien Tran, Selene K. Swanson, Laurence Florens, Michael P. Washburn, Samara L. Reck-Peterson
2017 · doi:10.1101/143743
preprint OA: closed
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Abstract

ABSTRACT In human cells, cytoplasmic dynein-1 is essential for long-distance transport of many cargos, including organelles, RNAs, proteins, and viruses, towards microtubule minus ends. To understand how a single motor achieves cargo specificity, we identified the human dynein interactome or “transportome” by attaching a promiscuous biotin ligase (“BioID”) to seven components of the dynein machinery, including a subunit of the essential cofactor dynactin. This method reported spatial information about the large cytosolic dynein/dynactin complex in living cells. To achieve maximal motile activity and to bind its cargos, human dynein/dynactin requires “activators”, of which only five have been described. We developed methods to identify new activators in our BioID data, and discovered that ninein and ninein-like are a new family of dynein activators. Analysis of the protein interactomes for six activators, including ninein and ninein-like, suggests that each dynein activator has multiple cargos.

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