Zyxin phosphorylation at serine 142 modulates the zyxin head-tail interaction to alter cell-cell adhesion
Zyxin phosphorylation at serine 142 modulates the zyxin head-tail interaction to alter cell-cell adhesion
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DOI：
10.1016/j.bbrc.2010.12.058
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发表时间：
2011-01-21
影响因子：
3.1
通讯作者：
Hansen, Marc D. H.
中科院分区：
文献类型：
--
作者：
Call, Greg S.;Chung, Jarom Y.;Hansen, Marc D. H.
Zyxin是一种肌动蛋白调节蛋白，其集中在肌动蛋白-膜结合位点，特别是细胞连接处。Zyxin通过结合VASP参与肌动蛋白动力学，这种相互作用通过富含脯氨酸的N-末端ActA重复发生。在ActA重复序列处或附近的N-末端LIM结构域的分子内缔合可以防止VASP和其他结合配偶体结合全长zyxin。这种头尾相互作用可能解释了细胞如何调节zyxin在肌动蛋白动力学、细胞粘附和细胞迁移中的功能。由于zyxin通过LIM结构域与几个伴侣结合需要磷酸化，因此zyxin磷酸化可能会改变头-尾相互作用，从而改变zyxin活性。在这里，我们表明，zyxin点突变体在一个已知的磷酸化位点，丝氨酸142，改变zyxin片段的能力，直接结合一个单独的zyxin LIM结构域片段蛋白。此外，zyxin磷酸模拟物突变体的表达导致MDCK细胞的细胞-细胞接触的定位增加，并产生细胞表型，即不能分解细胞-细胞接触，精确地像通过表达缺乏整个调节性LIM结构域区域的zyxin突变体产生的那样。这些数据表明，在丝氨酸142处的zyxin磷酸化导致头-尾相互作用的释放，改变了zyxin在细胞-细胞接触处的活性。(C)2010爱思唯尔公司All rights reserved.
Zyxin is an actin regulatory protein that is concentrated at sites of actin-membrane association, particularly cell junctions. Zyxin participates in actin dynamics by binding VASP, an interaction that occurs via proline-rich N-terminal ActA repeats. An intramolecular association of the N-terminal LIM domains at or near the ActA repeats can prevent VASP and other binding partners from binding full-length zyxin. Such a head-tail interaction likely accounts for how zyxin function in actin dynamics, cell adhesion, and cell migration can be regulated by the cell. Since zyxin binding to several partners, via the LIM domains, requires phosphorylation, it seems likely that zyxin phosphorylation might alter the head-tail interaction and, thus, zyxin activity. Here we show that zyxin point mutants at a known phosphorylation site, serine 142, alter the ability of a zyxin fragment to directly bind a separate zyxin LIM domains fragment protein. Further, expression of the zyxin phosphomimetic mutant results in increased localization to cell-cell contacts of MDCK cells and generates a cellular phenotype, namely inability to disassemble cell-cell contacts, precisely like that produced by expression of zyxin mutants that lack the entire regulatory LIM domain region. These data suggest that zyxin phosphorylation at serine 142 results in release of the head-tail interaction, changing zyxin activity at cell-cell contacts. (C) 2010 Elsevier Inc. All rights reserved.