Lissencephaly-1 is a context-dependent regulator of the human dynein complex
- MRC Laboratory of Molecular Biology, United Kingdom
Abstract
The cytoplasmic dynein-1 (dynein) motor plays a central role in microtubule organisation and cargo transport. These functions are spatially regulated by association of dynein and its accessory complex dynactin with dynamic microtubule plus ends. Here, we elucidate in vitro the roles of dynactin, end-binding protein-1 (EB1) and Lissencephaly-1 (LIS1) in the interaction of end tracking and minus end-directed human dynein complexes with these sites. LIS1 promotes dynactin-dependent tracking of dynein on both growing and shrinking plus ends. LIS1 also increases the frequency and velocity of processive dynein movements that are activated by complex formation with dynactin and a cargo adaptor. This stimulatory effect of LIS1 contrasts sharply with its documented ability to inhibit the activity of isolated dyneins. Collectively, our findings shed light on how mammalian dynein complexes associate with dynamic microtubules and help clarify how LIS1 promotes the plus end localisation and cargo transport functions of dynein in vivo.
Article and author information
Author details
Funding
Medical Research Council (MC_U105178790)
- Simon L Bullock
Deutsche Forschungsgemeinschaft (BA 5802/1-1)
- Janina Baumbach
Boehringer Ingelheim Fonds
- Ha Thi Hoang
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2017, Baumbach 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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Lissencephaly-1 is a context-dependent regulator of the human dynein complex
eLife 6:e21768.
https://doi.org/10.7554/eLife.21768
