mTORC2 通过 cAMP 和 RhoA 依赖的方式调节中性粒细胞趋化性。
mTORC2 regulates neutrophil chemotaxis in a cAMP- and RhoA-dependent fashion.
机构信息
Center for Cancer Research, NCI, NIH, Bethesda, MD 20892, USA.
出版信息
Dev Cell. 2010 Dec 14;19(6):845-57. doi: 10.1016/j.devcel.2010.11.004.
We studied the role of the target of rapamycin complex 2 (mTORC2) during neutrophil chemotaxis, a process that is mediated through the polarization of actin and myosin filament networks. We show that inhibition of mTORC2 activity, achieved via knock down (KD) of Rictor, severely inhibits neutrophil polarization and directed migration induced by chemoattractants, independently of Akt. Rictor KD also abolishes the ability of chemoattractants to induce cAMP production, a process mediated through the activation of the adenylyl cyclase 9 (AC9). Cells with either reduced or higher AC9 levels also exhibit specific and severe tail retraction defects that are mediated through RhoA. We further show that cAMP is excluded from extending pseudopods and remains restricted to the cell body of migrating neutrophils. We propose that the mTORC2-dependent regulation of MyoII occurs through a cAMP/RhoA-signaling axis, independently of actin reorganization during neutrophil chemotaxis.
我们研究了雷帕霉素复合物 2（mTORC2）在中性粒细胞趋化作用中的作用，这一过程是通过肌动蛋白和肌球蛋白丝网络的极化来介导的。我们表明，通过敲低 Rictor 来抑制 mTORC2 活性，严重抑制了趋化因子诱导的中性粒细胞极化和定向迁移，这一过程独立于 Akt。Rictor KD 还消除了趋化因子诱导 cAMP 产生的能力，这一过程是通过激活腺苷酸环化酶 9（AC9）来介导的。AC9 水平降低或升高的细胞也表现出特定的和严重的尾部回缩缺陷，这是通过 RhoA 介导的。我们进一步表明，cAMP 被排除在延伸伪足之外，并仍然局限于迁移中性粒细胞的细胞体。我们提出，mTORC2 依赖的 MyoII 调节发生在 cAMP/RhoA 信号轴上，这一过程独立于中性粒细胞趋化过程中的肌动蛋白重排。
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