The Human Cytoplasmic Dynein Interactome Reveals Novel Activators Of Motility

Redwine, W. B.; DeSantis, M. E.; Hollyer, I.; Htet, Z. M.; Tran, P. T.; Swanson, S. K.; Florens, L.; Washburn, M. P.; Reck-Peterson, S. L.

doi:10.1101/143743

bioRxiv · 10.1101/143743

The Human Cytoplasmic Dynein Interactome Reveals Novel Activators Of Motility

Redwine, W. B.·DeSantis, M. E.·Hollyer, I.·Htet, Z. M.·Tran, P. T.·Swanson, S. K.·Florens, L.·Washburn, M. P.·Reck-Peterson, S. L.

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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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Redwine, W. B., DeSantis, M. E., Hollyer, I., Htet, Z. M., Tran, P. T., Swanson, S. K., Florens, L., Washburn, M. P., Reck-Peterson, S. L.. 2017-05-30. The Human Cytoplasmic Dynein Interactome Reveals Novel Activators Of Motility. https://doi.org/10.1101/143743

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