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 AMP. AMPK is activated by various cellular stresses that inhibit ATP production or stimulate ATP consumption. In addition to its role in metabolism, AMPK has recently been reported to reshape cells by regulating cell polarity and division. 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.
authors.affiliation: Division of Cardiovascular Medicine, National Cardiovascular Center Research Institute Suita, Osaka 565-8565, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakano
authors.forename: Hisakazu
authors.initials: H
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Watanabe
authors.forename: Kyung-Duk
authors.initials: KD
authors.lastname: Min
authors.forename: Satoru
authors.initials: S
authors.lastname: Yamazaki
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Asano
authors.forename: Osamu
authors.initials: O
authors.lastname: Seguchi
authors.forename: Shuichiro
authors.initials: S
authors.lastname: Higo
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Shintani
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Asanuma
authors.forename: Masanori
authors.initials: M
authors.lastname: Asakura
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Minamino
authors.forename: Kozo
authors.initials: K
authors.lastname: Kaibuchi
authors.forename: Naoki
authors.initials: N
authors.lastname: Mochizuki
authors.forename: Masafumi
authors.initials: M
authors.lastname: Kitakaze
authors.forename: Seiji
authors.initials: S
authors.lastname: Takashima
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D016764:Cell Polarity; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism; D009363:Neoplasm Proteins / Q000378:metabolism*; D010641:Phenotype; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism; D015398:Signal Transduction; D014404:Tubulin / Q000378:metabolism
chemical_list: D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D014404:Tubulin; C076744:cytoplasmic linker protein 170; D011494:Protein Kinases; D055372:AMP-Activated Protein Kinases