Plasma membrane (PM) curvature defines cell shape and intracellular organelle morphologies and is a fundamental cell property. Growth/proliferation is more stimulated in flatter cells than the same cells in elongated shapes. PM-anchored K-Ras small GTPase regulates cell growth/proliferation and plays key roles in cancer. The lipid-anchored K-Ras form nanoclusters selectively enriched with specific phospholipids, such as phosphatidylserine (PS), for efficient effector recruitment and activation. K-Ras function may, thus, be sensitive to changing lipid distribution at membranes with different curvatures. Here, we used complementary methods to manipulate membrane curvature of intact/live cells, native PM blebs, and synthetic liposomes. We show that the spatiotemporal organization and signaling of an oncogenic mutant K-Ras ^G12V favor flatter membranes with low curvature. Our findings are consistent with the more stimulated growth/proliferation in flatter cells. Depletion of endogenous PS abolishes K-Ras ^G12V PM curvature sensing. In cells and synthetic bilayers, only mixed-chain PS species, but not other PS species tested, mediate K-Ras ^G12V membrane curvature sensing. Thus, K-Ras nanoclusters act as relay stations to convert mechanical perturbations to mitogenic signaling.

中文翻译：

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脂质锚定的K-Ras小GTPase的膜曲率传感。

质膜（PM）曲率定义了细胞的形状和细胞内细胞器的形态，是一种基本的细胞特性。在扁平细胞中比在细长形状的相同细胞中更能刺激生长/增殖。PM锚定的K-Ras小GTP酶调节细胞的生长/增殖，并在癌症中发挥关键作用。脂质锚定的K-Ras形成纳米簇，选择性富集了特定的磷脂，例如磷脂酰丝氨酸（PS），可有效募集和激活效应子。因此，K-Ras功能可能对改变曲率不同的膜上的脂质分布敏感。在这里，我们使用互补方法来操纵完整/活细胞，天然PM气泡和合成脂质体的膜曲率。我们表明，时空组织和致癌突变体K Ras的信号。 ^G12V 倾向于使用低曲率的扁平膜。我们的发现与扁平细胞中更受刺激的生长/增殖相符。内源性PS的耗尽消除了K-Ras ^G12V PM曲率感测。在细胞和合成双层膜中，只有混合链PS物种（而不是其他受测试的PS物种）介导K-Ras ^G12V膜曲率传感。因此，K-Ras纳米簇充当中继站，将机械扰动转换为有丝分裂信号。