Department of Biology, Northeastern University, Boston, MA 02115.
Center for Molecular Medicine, Molecular Cancer Research Section, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, the Netherlands.
Mol Biol Cell. 2020 Jul 1;31(14):1486-1497. doi: 10.1091/mbc.E20-04-0236. Epub 2020 May 6.
Actomyosin-based contractility in smooth muscle and nonmuscle cells is regulated by signaling through the small GTPase Rho and by calcium-activated pathways. We use the myoepithelial cells of the spermatheca to study the mechanisms of coordinated myosin activation in vivo. Here, we show that redox signaling modulates RHO-1/Rho activity in this contractile tissue. Exogenously added as well as endogenously generated hydrogen peroxide decreases spermathecal contractility by inhibition of RHO-1, which depends on a conserved cysteine in its nucleotide binding site (C20). Further, we identify an endogenous gradient of HO across the spermathecal tissue, which depends on the activity of cytosolic superoxide dismutase, SOD-1. Collectively, we show that SOD-1-mediated HO production regulates the redox environment and fine tunes Rho activity across the spermatheca through oxidation of RHO-1 C20.
基于肌球蛋白的收缩性在平滑肌和非肌肉细胞中受通过小 GTPase Rho 的信号和钙激活途径调节。我们使用精囊的肌上皮细胞来研究体内协调肌球蛋白激活的机制。在这里，我们表明氧化还原信号调节这种收缩组织中的 RHO-1/Rho 活性。外源性添加和内源性产生的过氧化氢通过抑制 RHO-1 来降低精囊的收缩性，这取决于其核苷酸结合位点（C20）中的保守半胱氨酸。此外，我们鉴定了 HO 在整个精囊组织中的内源性梯度，这取决于细胞质超氧化物歧化酶 SOD-1 的活性。总的来说，我们表明 SOD-1 介导的 HO 产生通过氧化 RHO-1 C20 来调节氧化还原环境并微调整个精囊中的 Rho 活性。
