TIP150 interacts with and targets MCAK at the microtubule plus ends.
The microtubule (MT) cytoskeleton orchestrates the cellular plasticity and dynamics that underlie morphogenesis and cell division. Growing MT plus ends have emerged as dynamic regulatory machineries in which specialized proteins-called plus-end tracking proteins (+TIPs)-bind to and control the plus-end dynamics that are essential for cell division and migration. However, the molecular mechanisms underlying the plus-end regulation by +TIPs at spindle and astral MTs have remained elusive. Here, we show that TIP150 is a new +TIP that binds to end-binding protein 1 (EB1) in vitro and co-localizes with EB1 at the MT plus ends in vivo. Suppression of EB1 eliminates the plus-end localization of TIP150. Interestingly, TIP150 also binds to mitotic centromere-associated kinesin (MCAK), an MT depolymerase that localizes to the plus end of MTs. Suppression of TIP150 diminishes the plus-end localization of MCAK. Importantly, aurora B-mediated phosphorylation disrupts the TIP150-MCAK association in vitro. We reason that TIP150 facilitates the EB1-dependent loading of MCAK onto MT plus ends and orchestrates the dynamics at the plus end of MTs.
Jiang
Kai
K
Anhui Key Laboratory for Cellular Dynamics and Chemical Biology, University of Science and Technology of China, Hefei 230027, China.
Wang
Jianyu
J
Liu
Jing
J
Ward
Tarsha
T
Wordeman
Linda
L
Davidson
Alec
A
Wang
Fengsong
F
Yao
Xuebiao
X
D000595:Amino Acid Sequence; D002460:Cell Line; D006367:HeLa Cells; D006801:Humans; D007150:Immunohistochemistry; D016547:Kinesins / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding; D017386:Sequence Homology, Amino Acid; D014162:Transfection
C091489:KIF2C protein, human; C500985:MAPRE1 protein, human; D008869:Microtubule-Associated Proteins; D016547:Kinesins