In mitosis, chromosomes are more than passive passengers segregated by spindle microtubules. They actively drive s pindle ass embly by producing the GTP bound form of the RanGTPase in their vicinity. Ran-GTP binds to the heterodimeric nuclear transport receptor importin α/β and dissociates nuclear localization signal (NLS)-containing proteins from the importins. Liberated NLS proteins, such as TPX2, play distinct roles in spindle microtubule assembly. To comprehensively identify novel Ran-regulated spindle assembly factors, I sequentially purified NLS proteins and microtubule-associated proteins (MAPs) from Xenopus egg extracts, and identified ~150 proteins (Yokoyama et al., 2009). Of those, the chromatin-remodeling ATPases, CHD4 and ISWI, surprisingly function as bona-fide MAPs in vitro. Both proteins dissociate from chromatin in mitosis and re-localize to the spindle. Their mitotic functions are, however, temporally distinct: CHD4 is a Ran-GTP dependent microtubule stabilizer essential for spindle assembly (Yokoyama et al., in press), while ISWI specifically stabilizes microtubules in anaphase to maintain the spindle and ensure chromosome segregation (Yokoyama et al., 2009). The functions of CHD4 and ISWI are independent of chromatin remodeling, and are conserved in Xenopus egg extracts and human cells. My data establish a new principle that chromosomes drive not only spindle assembly but also other mitotic processes essential for their own segregation. The direct function of chromosomes is to produce Ran-GTP and additionally to release important mitotic regulators from them.
Dr.Hideki Yokoyama (ZMBH) New mitotic regulators released from chromatin
New mitotic regulators released from chromatin
2013.08.26 15:51
16:00-
片平・生命科学プロジェクト研究棟 1階講義室A
Dr. Hideki Yokoyama
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH),
DKFZ-ZMBH Alliance , Heidelberg, Germany
Zentrum für Molekulare Biologie der Universität Heidelberg (ZMBH),
DKFZ-ZMBH Alliance , Heidelberg, Germany
生命科学研究科発生ダイナミクス分野 杉本亜砂子
e-mail:asugimoto*m.tohoku.ac.jp(*を@に置き換えてください)
電話:022-217-6194
e-mail:asugimoto*m.tohoku.ac.jp(*を@に置き換えてください)
電話:022-217-6194