Kodama Atsuko, Karakesisoglou Iakowos, Wong Ellen, Vaezi Alec, Fuchs Elaine
Howard Hughes Medical Institute, Laboratory of Mammalian Cell Biology and Development, The Rockefeller University, New York, NY 10021, USA.
Cell. 2003 Oct 31;115(3):343-54. doi: 10.1016/s0092-8674(03)00813-4.
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.
ACF7是细胞骨架交联蛋白光谱斑蛋白家族的成员，具有肌动蛋白和微管结合结构域。在此，我们表明ACF7是微管-肌动蛋白动力学的重要整合因子。在内胚层细胞中，ACF7沿微管结合，但在极化时集中于微管远端和细胞边界。在缺乏ACF7的情况下，微管仍能结合EB1和CLIP170，但不再沿极化的肌动蛋白束生长，也不会在富含肌动蛋白的皮质位点处暂停和锚定。结果是微管稳定性降低、长度变长、细胞质轨迹偏斜且动态不稳定性改变。在受伤时，ACF7基因敲除培养物激活极化信号，但无法维持这些信号并协调迁移。挽救这些缺陷需要ACF7的肌动蛋白和微管结合结构域。因此，光谱斑蛋白对于控制微管动力学以及加强微管与极化F-肌动蛋白之间的连接很重要，从而使细胞极化和协调的细胞运动得以维持。
