Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue

Hélène Henrie; Dalal Bakhos-Douaihy; Isabelle Cantaloube; Antoine Pilon; Maya Talantikite; Virginie Stoppin-Mellet; Anita Baillet; Christian Poüs; Béatrice Benoit

doi:10.1083/jcb.201909093

Stress-induced phosphorylation of CLIP-170 by JNK promotes microtubule rescue

J Cell Biol. 2020 Jul 6;219(7):e201909093. doi: 10.1083/jcb.201909093.

Authors

Affiliations

¹ Université Paris-Saclay, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1193, Châtenay-Malabry, France.
² Département de Biochimie, Hormonologie et Suivi Thérapeutique, Département Médico-Universitaire BioGeM, Assistance Publique - Hôpitaux de Paris Sorbonne Université, Paris, France.
³ Grenoble Institut des Neurosciences, Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1216, Université Grenoble Alpes, Grenoble, France.
⁴ Biochimie-Hormonologie, Assistance Publique - Hôpitaux de Paris Université Paris-Saclay, Clamart, France.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Anisomycin / pharmacology
Cell Line
Fibroblasts / drug effects
Fibroblasts / metabolism
Fibroblasts / radiation effects
Fibroblasts / ultrastructure
Gene Expression Regulation
HeLa Cells
Humans
MAP Kinase Kinase 4 / genetics*
MAP Kinase Kinase 4 / metabolism
Mice
Microtubule-Associated Proteins / antagonists & inhibitors
Microtubule-Associated Proteins / genetics*
Microtubule-Associated Proteins / metabolism
Microtubules / drug effects
Microtubules / metabolism*
Microtubules / radiation effects
Microtubules / ultrastructure
Neoplasm Proteins / antagonists & inhibitors
Neoplasm Proteins / genetics*
Neoplasm Proteins / metabolism
Phosphorylation / drug effects
Phosphorylation / radiation effects
Protein Kinase Inhibitors / pharmacology
Signal Transduction
Sodium Chloride / pharmacology
Stress, Physiological / genetics*
Ultraviolet Rays

Substances

Microtubule-Associated Proteins
Neoplasm Proteins
Protein Kinase Inhibitors
cytoplasmic linker protein 170
Sodium Chloride
Anisomycin
MAP Kinase Kinase 4