研究人员利用条件性基因打靶（conditional gene targeting）来去除小鼠皮肤的ACF7表达。结果发现，ACF7的不足会导致表皮迁移的损害。科学家们的发现揭示了ACF7在伤口愈合以及表皮迁移方面的关键作用，这与ACF7、微管、丝状肌动蛋白以及焦点黏着斑（focal adhesion FA）之间的联系有关。通过解除这种联系，研究人员发现这对于控制FA的组装以及动力学很重要。而令人惊讶的是，ACF7结合微管、丝状肌动蛋白、末端蛋白的能力并不足以挽回野生型ACF7的全部功能。结果表明，ACF7能起到ATP酶的作用，并且更重要的是，ACF7更像一种肌动蛋白调节ATP酶，而非微管调节或钙调节ATP酶。

     因此科学家认为，尽管对于血影斑蛋白家族的了解还很少，以上发现揭示了它们是如何进化成为独特的调节肌动蛋白-微管相互作用的大分子物质的。此外，ACF7在细胞运动过程中建立和维持正确细胞骨架协调作用的过程也得到了体现。文章最后作者表示，他们的发现为更进一步研究ACF7在肌动蛋白、微管细胞骨架网之间的协调作用铺平了道路。（生物谷Bioon.com）

生物谷推荐原始出处：

Cell，Vol 135, 137-148, 03 October 2008，Xiaoyang Wu, Atsuko Kodama, and Elaine Fuchs

ACF7 Regulates Cytoskeletal-Focal Adhesion Dynamics and Migration and Has ATPase Activity

Xiaoyang Wu,1 Atsuko Kodama,1,2 and Elaine Fuchs1,

1 The Howard Hughes Medical Institute and Laboratory of Mammalian Cell Biology and Development, Rockefeller University, New York, NY 10065, USA

Coordinated interactions between microtubule (MT) and actin cytoskeletons are involved in many polarized cellular processes. Spectraplakins are enormous (>500 kDa) proteins able to bind both MTs and actin filaments (F-actin) directly. To elucidate the physiological significance and functions of mammalian spectraplakin ACF7, we've conditionally targeted it in skin epidermis. Intriguingly, ACF7 deficiency compromises the targeting of microtubules along F-actin to focal adhesions (FAs), stabilizes FA-actin networks, and impairs epidermal migration. Exploring underlying mechanisms, we show that ACF7's binding domains for F-actin, MTs, and MT plus-end proteins are not sufficient to rescue the defects in FA-cytoskeletal dynamics and migration functions of ACF7 null keratinocytes. We've uncovered an intrinsic actin-regulated ATPase domain in ACF7 and demonstrate that it is both functional and essential for these roles. Our findings provide insight into the functions of this important cytoskeletal crosslinking protein in regulating dynamic interactions between MTs and F-actin to sustain directional cell movement.