AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation.
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.
Nakano
Atsushi
A
Division of Cardiovascular Medicine, National Cardiovascular Center Research Institute Suita, Osaka 565-8565, Japan.
Kato
Hisakazu
H
Watanabe
Takashi
T
Min
Kyung-Duk
KD
Yamazaki
Satoru
S
Asano
Yoshihiro
Y
Seguchi
Osamu
O
Higo
Shuichiro
S
Shintani
Yasunori
Y
Asanuma
Hiroshi
H
Asakura
Masanori
M
Minamino
Tetsuo
T
Kaibuchi
Kozo
K
Mochizuki
Naoki
N
Kitakaze
Masafumi
M
Takashima
Seiji
S
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
D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D014404:Tubulin; C076744:cytoplasmic linker protein 170; D011494:Protein Kinases; D055372:AMP-Activated Protein Kinases