Ampk controls the speed of microtubule polymerization and directional cell migration through clip-170 phosphorylation

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 division3,4,5,6.

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. Access through your institution Buy or subscribe This is a preview of subscription content, access via your

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YEAST DIS1 IS AN UNCONVENTIONAL TOG/XMAP215 THAT INDUCES MICROTUBULE CATASTROPHE TO DRIVE CHROMOSOME PULLING Article Open access 26 November 2022 REFERENCES * Yeh, L. A., Lee, K. H. &

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_Mol. Biol. Cell_ 16, 5334–5345 (2005). Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank M. Amano and S. Fukuhara for helpful discussions,

and M. Koyama (Olympus Corporation) for technical advice regarding microscopy. This research was supported by: a Grants-in-Aid from the Ministry of Health, Labour and Welfare of Japan;

Grants-in-Aid from the Ministry of Education, Culture, Sports, Science and Technology of Japan; grants from the Japan Heart Foundation; grants from the Japan Cardiovascular Research

Foundation; a grant from the Japan Society for the Promotion of Science; a grant from the Mochida Memorial Foundation for Medical and Pharmaceutical Research; and a Grant-in-Aid from the

Japan Medical Association. AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * Division of Cardiovascular Medicine, National Cardiovascular Center Research Institute Suita, Osaka, 565-8565, Japan

Atsushi Nakano, Kyung-Duk Min, Satoru Yamazaki, Osamu Seguchi, Hiroshi Asanuma, Masanori Asakura & Masafumi Kitakaze * Department of Structural Analysis, National Cardiovascular Center,

Research Institute Suita, Osaka, 565-8565, Japan Naoki Mochizuki * Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine Suita, Osaka, 565-0871, Japan Hisakazu

Kato, Kyung-Duk Min, Yoshihiro Asano, Shuichiro Higo, Yasunori Shintani, Tetsuo Minamino & Seiji Takashima * Department of Molecular Cardiology, Osaka University Graduate School of

Medicine Suita, Osaka, 565-0871, Japan Atsushi Nakano, Hisakazu Kato, Yoshihiro Asano & Seiji Takashima * Institute for Advanced Research, Nagoya University Graduate School of Medicine,

Nagoya, 466-8550, Aichi, Japan Takashi Watanabe * Department of Cell Pharmacology, Nagoya University Graduate School of Medicine, Nagoya, 466-8550, Aichi, Japan Takashi Watanabe & Kozo

Kaibuchi Authors * Atsushi Nakano View author publications You can also search for this author inPubMed Google Scholar * Hisakazu Kato View author publications You can also search for this

author inPubMed Google Scholar * Takashi Watanabe View author publications You can also search for this author inPubMed Google Scholar * Kyung-Duk Min View author publications You can also

search for this author inPubMed Google Scholar * Satoru Yamazaki View author publications You can also search for this author inPubMed Google Scholar * Yoshihiro Asano View author

publications You can also search for this author inPubMed Google Scholar * Osamu Seguchi View author publications You can also search for this author inPubMed Google Scholar * Shuichiro Higo

View author publications You can also search for this author inPubMed Google Scholar * Yasunori Shintani View author publications You can also search for this author inPubMed Google Scholar

* Hiroshi Asanuma View author publications You can also search for this author inPubMed Google Scholar * Masanori Asakura View author publications You can also search for this author

inPubMed Google Scholar * Tetsuo Minamino View author publications You can also search for this author inPubMed Google Scholar * Kozo Kaibuchi View author publications You can also search

for this author inPubMed Google Scholar * Naoki Mochizuki View author publications You can also search for this author inPubMed Google Scholar * Masafumi Kitakaze View author publications

You can also search for this author inPubMed Google Scholar * Seiji Takashima View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS A.N. designed

and conducted the study, performed most of the experiments, and wrote the manuscript; S.T. designed and conducted the study, performed the biochemical experiments and wrote the manuscript;

H.K. carried out immunoblot analysis; K.M. independently counted the number of cells; S.Y. helped to generate the plasmids; Y.A., O.S., S.H., Y.S., H.A., M.A. and T.M. discussed the results

and reviewed the manuscript; T.W. and K.K. generated and provided antibodies and Vero cells and reviewed the manuscript; N.M. conducted and supported the biological experiments and wrote the

manuscript; M.K. supervised all work. CORRESPONDING AUTHOR Correspondence to Seiji Takashima. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing financial interests.

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Supplementary Movie 8 (MOV 9470 kb) RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE CITE THIS ARTICLE Nakano, A., Kato, H., Watanabe, T. _et al._ AMPK controls the speed

of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation. _Nat Cell Biol_ 12, 583–590 (2010). https://doi.org/10.1038/ncb2060 Download citation *

Received: 04 March 2010 * Accepted: 29 April 2010 * Published: 23 May 2010 * Issue Date: June 2010 * DOI: https://doi.org/10.1038/ncb2060 SHARE THIS ARTICLE Anyone you share the following

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