We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Regulation of in vivo dynein force production by CDK5 and 14-3-3ε and KIAA0528.
- Authors
Chapman, Dail E.; Reddy, Babu J. N.; Huy, Bunchhin; Bovyn, Matthew J.; Cruz, Stephen John S.; Al-Shammari, Zahraa M.; Han, Han; Wang, Wenqi; Smith, Deanna S.; Gross, Steven P.
- Abstract
Single-molecule cytoplasmic dynein function is well understood, but there are major gaps in mechanistic understanding of cellular dynein regulation. We reported a mode of dynein regulation, force adaptation, where lipid droplets adapt to opposition to motion by increasing the duration and magnitude of force production, and found LIS1 and NudEL to be essential. Adaptation reflects increasing NudEL-LIS1 utilization; here, we hypothesize that such increasing utilization reflects CDK5-mediated NudEL phosphorylation, which increases the dynein-NudEL interaction, and makes force adaptation possible. We report that CDK5, 14-3-3ε, and CDK5 cofactor KIAA0528 together promote NudEL phosphorylation and are essential for force adaptation. By studying the process in COS-1 cells lacking Tau, we avoid confounding neuronal effects of CDK5 on microtubules. Finally, we extend this in vivo regulatory pathway to lysosomes and mitochondria. Ultimately, we show that dynein force adaptation can control the severity of lysosomal tug-of-wars among other intracellular transport functions involving high force. Dynein plays roles in vesicular, organelle, chromosomal and nuclear transport but so far it is unclear how dynein activity in cells is regulated. Here authors study several dynein cofactors and their role in force adaptation of dynein during lipid droplet, lysosomal, and mitochondrial transport.
- Publication
Nature Communications, 2019, Vol 10, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-018-08110-z