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

doi:10.1038/ncb2060

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 journal › Article › peer-review

165 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 division^3-6. 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 language	English
Pages (from-to)	583-590
Number of pages	8
Journal	Nature Cell Biology
Volume	12
Issue number	6
DOIs	https://doi.org/10.1038/ncb2060
Publication status	Published - 06-2010
Externally published	Yes

All Science Journal Classification (ASJC) codes

Cell Biology

Access to Document

10.1038/ncb2060

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

@article{03c5062da344450ea04c4d0bc022a4d9,

title = "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 division3-6. 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.",

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

note = "Funding Information: 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.",

year = "2010",

month = jun,

doi = "10.1038/ncb2060",

language = "English",

volume = "12",

pages = "583--590",

journal = "Nature Cell Biology",

issn = "1465-7392",

publisher = "Nature Research",

number = "6",

}

Nakano, A, Kato, H, Watanabe, T, Min, KD, 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, vol. 12, no. 6, pp. 583-590. https://doi.org/10.1038/ncb2060

TY - JOUR

T1 - AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation

AU - Nakano, Atsushi

AU - Kato, Hisakazu

AU - Watanabe, Takashi

AU - Min, Kyung Duk

AU - Yamazaki, Satoru

AU - Asano, Yoshihiro

AU - Seguchi, Osamu

AU - Higo, Shuichiro

AU - Shintani, Yasunori

AU - Asanuma, Hiroshi

AU - Asakura, Masanori

AU - Minamino, Tetsuo

AU - Kaibuchi, Kozo

AU - Mochizuki, Naoki

AU - Kitakaze, Masafumi

AU - Takashima, Seiji

N1 - Funding Information: 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.

PY - 2010/6

Y1 - 2010/6

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=77953121697&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77953121697&partnerID=8YFLogxK

U2 - 10.1038/ncb2060

DO - 10.1038/ncb2060

M3 - Article

C2 - 20495555

AN - SCOPUS:77953121697

SN - 1465-7392

VL - 12

SP - 583

EP - 590

JO - Nature Cell Biology

JF - Nature Cell Biology

IS - 6

ER -

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

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this