The human cytoplasmic dynein interactome reveals novel activators of motility
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 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.
Article and author information
Author details
Funding
National Institutes of Health (R01GM121772)
- Willam B Redwine
- Phuoc Tien Tran
- Samara L Reck-Peterson
Howard Hughes Medical Institute (Faculty Scholar)
- Morgan E DeSantis
- Samara L Reck-Peterson
Simons Foundation (Faculty Scholar)
- Morgan E DeSantis
- Samara L Reck-Peterson
National Institutes of Health (R01GM107214)
- Ian Hollyer
- Samara L Reck-Peterson
Jane Coffin Childs Memorial Fund for Medical Research
- Morgan E DeSantis
National Science Foundation
- Zaw Min Htet
Stowers Institute for Medical Research
- Selene K Swanson
- Laurence Florens
- Michael P Washburn
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Redwine et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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