Identification And Functional Analysis Of A Novel Microtubule Plus-end Tracking Protein-TIP150

The microtubule(MT) cytoskeleton orchestrates cellular plasticity and dynamics underlying morphogenesis and cell division.Growing MT plus-ends have emerged as dynamic regulatory machinery in which specialized proteins,called plus-end-tracking proteins(+TIPs),bind and govern the plus-end dynamics essential for cell division and migration.However,the molecular mechanisms underlying the plus-end regulation by +TIPs at spindle and astral MT have remained elusive.Here we show that TIP150 is a novel +TIP.TIP150 binds to 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 MCAK,a MT-depolymerase localizing to the plus-end of MT.Suppression of TIP150 diminishes the plus-end localization of MCAK.Importantly,Aurora B-mediated phosphorylation disrupts TIP150-MCAK association in vitro.I reason that TIP150 facilitates the EB1-dependent loading of MCAK onto MT plus-ends and orchestrates the dynamics at the plus-end of MTs.My preliminary results also indicate that TIP150 is a tetramer and may play an important role in crosslinking different types of cytoskeleton,which suggest a possible function of TIP150 in the process of cell migration,astral microtubule position et al.