Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue
| Autor: | Maya Talantikite, Antoine Pilon, Dalal Bakhos-Douaihy, Béatrice Benoit, Anita Baillet, Christian Poüs, Hélène Henrie, Isabelle Cantaloube, Virginie Stoppin-Mellet |
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| Rok vydání: | 2019 |
| Předmět: |
MAP Kinase Kinase 4
Ultraviolet Rays education Sodium Chloride Microtubules Article Cell Line Mice Microtubule Stress Physiological Animals Humans cardiovascular diseases Phosphorylation Protein Kinase Inhibitors Cytoskeleton Regulation of gene expression biology Kinase Cell Biology Fibroblasts In vitro Cell biology Neoplasm Proteins surgical procedures operative Tubulin Gene Expression Regulation Cell culture biology.protein Signal transduction Microtubule-Associated Proteins Anisomycin HeLa Cells Signal Transduction |
| Zdroj: | The Journal of Cell Biology |
| ISSN: | 1540-8140 |
| Popis: | Upon stress, JNK stimulates microtubule dynamics in human epithelial cell lines. Henrie et al. show that JNK phosphorylates the rescue factor CLIP-170, increasing its retention frequency on the lattice behind comets, at locations that correspond to potential future rescue sites. The stress-induced c-Jun N-terminal kinase (JNK) controls microtubule dynamics by enhancing both microtubule growth and rescues. Here, we show that upon cell stress, JNK directly phosphorylates the microtubule rescue factor CLIP-170 in its microtubule-binding domain to increase its rescue-promoting activity. Phosphomimetic versions of CLIP-170 enhance its ability to promote rescue events in vitro and in cells. Furthermore, while phosphomimetic mutations do not alter CLIP-170’s capability to form comets at growing microtubule ends, both phosphomimetic mutations and JNK activation increase the occurrence of CLIP-170 remnants on the microtubule lattice at the rear of comets. As the CLIP-170 remnants, which are potential sites of microtubule rescue, display a shorter lifetime when CLIP-170 is phosphorylated, we propose that instead of acting at the time of rescue occurrence, CLIP-170 would rather contribute in preparing the microtubule lattice for future rescues at these predetermined sites. Graphical Abstract |
| Databáze: | OpenAIRE |
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