LIS1 is an essential cofactor for the assembly of the cytoplasmic dynein transport machinery. How LIS1 binding affects dynein motility was unclear. Single-molecule experiments reveal that Pac1 (the yeast homolog of LIS1) binding reduces dynein speed by slowing its detachment from microtubules and does not disrupt the mechanism by which it generates force.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$29.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$259.00 per year
only $21.58 per issue
Buy this article
- Purchase on Springer Link
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Markus, S. M., Marzo, M. G. & McKenney, R. J. New insights into the mechanism of dynein motor regulation by lissencephaly-1. eLife 9, 59737 (2020). A review that presents how Lis1 influences dynein-mediated transport.
Huang, J., Roberts, A. J., Leschziner, A. E. & Reck-Peterson, S. L. Lis1 acts as a "clutch" between the ATPase and microtubule-binding domains of the dynein motor. Cell 150, 975–986 (2012). A report that Lis1 slows dynein by increasing its affinity for microtubules.
Marzo, M. G., Griswold, J. M. & Markus, S. M. Pac1/LIS1 stabilizes an uninhibited conformation of dynein to coordinate its localization and activity. Nat. Cell Biol. 22, 559–569 (2020). This paper reports that Lis1 slows dynein by tethering it to the microtubule.
Toropova, K. et al. Lis1 regulates dynein by sterically blocking its mechanochemical cycle. eLife 3, 03372 (2014). This paper reports that Lis1 binding blocks the power stroke of dynein.
Rao, L., Berger, F., Nicholas, M. P. & Gennerich, A. Molecular mechanism of cytoplasmic dynein tension sensing. Nat. Commun. 10, 3332 (2019). This paper shows dynein’s responses to external forces are mediated by the sliding of the stalk coiled-coils.
Elshenawy, M. M. et al. Lis1 activates dynein motility by modulating its pairing with dynactin. Nat. Cell Biol. 22, 570–578 (2020).
Htet, Z. M. et al. LIS1 promotes the formation of activated cytoplasmic dynein-1 complexes. Nat. Cell Biol. 22, 518–525 (2020). References 6 and 7 show that Lis1 facilitates formation of dynein–dynactin-adaptor complexes.
Additional information
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
This is a summary of: Kusakci, E. et al. Lis1 slows force-induced detachment of cytoplasmic dynein from microtubules. Nat. Chem. Biol. https://doi.org/10.1038/s41589-023-01464-6 (2023).
Rights and permissions
About this article
Cite this article
LIS1 (Pac1) binding slows dissociation of dynein from microtubules. Nat Chem Biol 20, 408–409 (2024). https://doi.org/10.1038/s41589-023-01465-5
Published:
Issue Date:
DOI: https://doi.org/10.1038/s41589-023-01465-5
