Department of Cellular and Molecular Medicine, University of California, San Diego, United States; Department of Cell Biology, Harvard Medical School, Boston, United States
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
Ian Hollyer
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
Zaw Min Htet
Department of Cellular and Molecular Medicine, University of California, San Diego, United States; Biophysics Graduate Program, Harvard Medical School, Boston, United States
Phuoc Tien Tran
Department of Cellular and Molecular Medicine, University of California, San Diego, United States
Selene K Swanson
Stowers Institute for Medical Research, Kansas, United States
Laurence Florens
Stowers Institute for Medical Research, Kansas, United States
Stowers Institute for Medical Research, Kansas, United States; Department of Pathology and Laboratory Medicine, The University of Kansas Medical Center, Kansas, United States
Department of Cellular and Molecular Medicine, University of California, San Diego, United States; Division of Biological Sciences, Cell and Developmental Biology Section, University of California, San Diego, United States
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 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.
