ACF7: An essential integrator of microtubule dynamics

被引:263
作者
Kodama, A [1 ]
Karakesisoglou, L [1 ]
Wong, E [1 ]
Vaezi, A [1 ]
Fuchs, E [1 ]
机构
[1] Rockefeller Univ, Howard Hughes Med Inst, Lab Mammalian Cell Biol & Dev, New York, NY 10021 USA
关键词
D O I
10.1016/S0092-8674(03)00813-4
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
ACF7 is a member of the spectraplakin family of cytoskeletal crosslinking proteins possessing actin and microtubule binding domains. Here, we show that ACF7 is an essential integrator of MT-actin dynamics. In endodermal cells, ACF7 binds along microtubules but concentrates at their distal ends and at cell borders when polarized. In ACF7's absence, microtubules still bind EB1 and CLIP170, but they no longer grow along polarized actin bundles, nor do they pause and tether to actin-rich cortical sites. The consequences are less stable, long microtubules with skewed cytoplasmic trajectories and altered dynamic instability. In response to wounding, ACF7 null cultures activate polarizing signals, but fail to maintain them and coordinate migration. Rescue of these defects requires ACF7's actin and microtubule binding domains. Thus, spectraplakins are important for controlling microtubule dynamics and reinforcing links between microtubules and polarized F-actin, so that cellular polarization and coordinated cell movements can be sustained.
引用
收藏
页码:343 / 354
页数:12
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