AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation

Atsushi Nakano, Hisakazu Kato, Takashi Watanabe, Kyung Duk Min, Satoru Yamazaki, Yoshihiro Asano, Osamu Seguchi, Shuichiro Higo, Yasunori Shintani, Hiroshi Asanuma, Masanori Asakura, Tetsuo Minamino, Kozo Kaibuchi, Naoki Mochizuki, Masafumi Kitakaze, Seiji Takashima

Research output: Contribution to journalArticle

136 Citations (Scopus)

Abstract

AMP-activated protein kinase (AMPK) is an energy-sensing Ser/Thr protein kinase originally shown to be regulated by AMP1. AMPK is activated by various cellular stresses that inhibit ATP production or stimulate ATP consumption2. In addition to its role in metabolism, AMPK has recently been reported to reshape cells by regulating cell polarity and division3-6. However, the downstream targets of AMPK that participate in these functions have not been fully identified. Here, we show that phosphorylation of the microtubule plus end protein CLIP-170 by AMPK is required for microtubule dynamics and the regulation of directional cell migration. Both inhibition of AMPK and expression of a non-phosphorylatable CLIP-170 mutant resulted in prolonged and enhanced accumulation of CLIP-170 at microtubule tips, and slower tubulin polymerization. Furthermore, inhibition of AMPK impaired microtubule stabilization and perturbed directional cell migration. All of these phenotypes were rescued by expression of a phosphomimetic CLIP-170 mutant. Our results demonstrate, therefore, that AMPK controls basic cellular functions by regulating microtubule dynamics through CLIP-170 phosphorylation.

Original languageEnglish
Pages (from-to)583-590
Number of pages8
JournalNature Cell Biology
Volume12
Issue number6
DOIs
Publication statusPublished - 06-2010

All Science Journal Classification (ASJC) codes

  • Cell Biology

Fingerprint Dive into the research topics of 'AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation'. Together they form a unique fingerprint.

  • Cite this

    Nakano, A., Kato, H., Watanabe, T., Min, K. D., Yamazaki, S., Asano, Y., Seguchi, O., Higo, S., Shintani, Y., Asanuma, H., Asakura, M., Minamino, T., Kaibuchi, K., Mochizuki, N., Kitakaze, M., & Takashima, S. (2010). AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation. Nature Cell Biology, 12(6), 583-590. https://doi.org/10.1038/ncb2060