In vivo epidermal migration requires focal adhesion targeting of ACF7.
In vivo epidermal migration requires focal adhesion targeting of ACF7.
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DOI：
10.1038/ncomms11692
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发表时间：
2016-05-24
影响因子：
16.6
通讯作者：
Wu X
中科院分区：
文献类型：
--
作者：
Yue J;Zhang Y;Liang WG;Gou X;Lee P;Liu H;Lyu W;Tang WJ;Chen SY;Yang F;Liang H;Wu X
粘着斑的周转使细胞回缩，这对细胞迁移至关重要。哺乳动物的血影斑蛋白ACF7（肌动蛋白交联因子7）通过将微管正端导向粘着斑来促进粘着斑动力学。然而，ACF7的活性如何在时空上受到调控以实现微管对粘着斑的特异性引导，仍不清楚。为了探索潜在机制，我们解析了ACF7的NT（氨基末端）结构域的晶体结构，该结构域介导F - 肌动蛋白相互作用。结构分析确定了ACF7的钙调蛋白同源（CH）结构域上的一个关键酪氨酸残基，它被Src/FAK（粘着斑激酶）复合物磷酸化对ACF7与F - 肌动蛋白的结合至关重要。我们以皮肤表皮作为模型系统进一步证明，ACF7的磷酸化在体外和体内的粘着斑动力学以及表皮迁移中起着不可或缺的作用。总之，我们的研究结果为细胞运动过程中协调的细胞骨架动力学的分子机制提供了关键见解。
血影斑蛋白ACF7在粘着斑处与肌动蛋白结合，并将微管正端导向粘着斑，促进其解聚。在此，作者揭示ACF7被Src/FAK磷酸化，这在体外和体内调节肌动蛋白结合以及粘着斑动力学。
Turnover of focal adhesions allows cell retraction, which is essential for cell migration. The mammalian spectraplakin protein, ACF7 (Actin-Crosslinking Factor 7), promotes focal adhesion dynamics by targeting of microtubule plus ends towards focal adhesions. However, it remains unclear how the activity of ACF7 is regulated spatiotemporally to achieve focal adhesion-specific guidance of microtubule. To explore the potential mechanisms, we resolve the crystal structure of ACF7’s NT (amino-terminal) domain, which mediates F-actin interactions. Structural analysis leads to identification of a key tyrosine residue at the calponin homology (CH) domain of ACF7, whose phosphorylation by Src/FAK (focal adhesion kinase) complex is essential for F-actin binding of ACF7. Using skin epidermis as a model system, we further demonstrate that the phosphorylation of ACF7 plays an indispensable role in focal adhesion dynamics and epidermal migration in vitro and in vivo. Together, our findings provide critical insights into the molecular mechanisms underlying coordinated cytoskeletal dynamics during cell movement. The spectraplakin protein ACF7 binds to actin at focal adhesions and targets microtubule plus ends to focal adhesions, promoting their disassembly. Here the authors reveal that ACF7 is phosphorylated by Src/FAK, and this regulates actin binding and focal adhesion dynamics in vitro and in vivo.
DOI：
10.1083/jcb.126.2.285
发表时间：
1994-07
期刊：
The Journal of cell biology
影响因子：
--
作者：
Matsudaira P
通讯作者：
Matsudaira P