Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/C...Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/CLIP-170,Klp5/Kinesin-8,and Alpl4/XMAP215 reside at microtubule plus ends to regulate microtubule dynamics.In the fission yeast Schizosaccharomyces pombe,Tipi and Alpl4 serve as microtubule-stabilizing factors,while Klp5 functions oppositely as a catastrophe-promoting factor.Despite that Tipi has been shown to play a key role in restricting microtubule catastrophe to the cell end,how Tipi fulfills the role remains to be determined.Employing live-cell microscopy,we showed that the absence of Tip i impairs the localization of both Klp5 and Alpl4 at microtubule plus ends,but the absence of Klp5 prolongs the residence time of Tipi at microtubule plus ends.We further revealed that Klp5 accumulates behind Tip i at microtubule plus ends in a Tipl-dependent manner.In addition,artificially tethering Klp5 to microtubule plus ends promotes premature microtubule catastrophe,while tethering Alpl4 to microtubule plus ends in the cells lacking Tipi rescues the phenotype of short microtubules.These findings establish that Tipi restricts microtubule catastrophe to the cell end likely by spatially restricting the microtubule catastrophe activity of Klp5 and stabilizing Alpl4 at microtubule plus ends.Thus,the work demonstrates the orchestration of Tipi,Alpl4,and Klp5 in ensuring microtubule catastrophe at the cell end.展开更多
基金the National Key Research and Development Program of China(2018YFC1004700)the National Natural Science Foundation of China(91754106,31671406,31871350,and 31601095)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB190A0101)the Major/lnnovative Program of Development Foundation of Hefei Center for Physical Science and Technology(2017FXCX008)China’s 1000 Young Talents Recruitment Program.
文摘Spatial regulation of microtubule catastrophe is important for controlling microtubule length and consequently contributes to the proper establishment of cell polarity and cell growth.The+TIP proteins including Tipl/CLIP-170,Klp5/Kinesin-8,and Alpl4/XMAP215 reside at microtubule plus ends to regulate microtubule dynamics.In the fission yeast Schizosaccharomyces pombe,Tipi and Alpl4 serve as microtubule-stabilizing factors,while Klp5 functions oppositely as a catastrophe-promoting factor.Despite that Tipi has been shown to play a key role in restricting microtubule catastrophe to the cell end,how Tipi fulfills the role remains to be determined.Employing live-cell microscopy,we showed that the absence of Tip i impairs the localization of both Klp5 and Alpl4 at microtubule plus ends,but the absence of Klp5 prolongs the residence time of Tipi at microtubule plus ends.We further revealed that Klp5 accumulates behind Tip i at microtubule plus ends in a Tipl-dependent manner.In addition,artificially tethering Klp5 to microtubule plus ends promotes premature microtubule catastrophe,while tethering Alpl4 to microtubule plus ends in the cells lacking Tipi rescues the phenotype of short microtubules.These findings establish that Tipi restricts microtubule catastrophe to the cell end likely by spatially restricting the microtubule catastrophe activity of Klp5 and stabilizing Alpl4 at microtubule plus ends.Thus,the work demonstrates the orchestration of Tipi,Alpl4,and Klp5 in ensuring microtubule catastrophe at the cell end.