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首页> 外文期刊>Molecular and Cellular Biology >NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins
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NADPH Oxidase 1 Controls the Persistence of Directed Cell Migration by a Rho-Dependent Switch of α2/α3 Integrins

机译：NADPH氧化酶1通过α2/α3整合素的Rho依赖性开关控制定向细胞迁移的持久性。

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NADPH oxidase 1 (Nox1) is expressed mainly in colon epithelial cells and produces superoxide ions as a primary function. We showed that Nox1 knockdown inhibits directional persistence of migration on collagen I. This paper dissects the mechanism by which Nox1 affects the direction of colonic epithelial cell migration in a two-dimensional model. Transient activation of Nox1 during cell spreading on collagen 1 temporarily inactivated RhoA and led to efficient exportation of α2β1 integrin to the cell surface, which supported persistent directed migration. Nox1 knockdown led to a loss of directional migration which takes place through a RhoA-dependent α2/α3 integrin switch. Transient RhoA overactivation upon Nox1 inhibition led to transient cytoskeletal reorganization and increased cell-matrix contact associated with a stable increase in α3 integrin cell surface expression. Blocking of α3 integrin completely reversed the loss of directional persistence of migration. In this model, Nox1 would represent a switch between random and directional migration through RhoA-dependent integrin cell surface expression modulation.
机译：NADPH氧化酶1（Nox1）主要在结肠上皮细胞中表达，并产生超氧离子作为主要功能。我们表明，Nox1组合式抑制胶原I迁移的方向性持久性。本文剖析了Nox1影响二维模型中结肠上皮细胞迁移方向的机制。细胞在胶原蛋白1上扩散期间的瞬时激活Nox1暂时使RhoA失活，并导致α2β1整联蛋白有效出口到细胞表面，从而支持持续的定向迁移。 Nox1敲低导致方向迁移的损失，这是通过RhoA依赖的α2/α3整联蛋白开关发生的。 Nox1抑制后的瞬时RhoA过度活化导致瞬时细胞骨架重组和细胞-基质接触增加，从而使α3整联蛋白细胞表面表达稳定增加。阻断α3整联蛋白完全逆转了迁移方向持久性的丧失。在此模型中，Nox1将代表通过RhoA依赖性整联蛋白细胞表面表达调节在随机迁移和定向迁移之间进行转换。

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