TY - JOUR T1 - Membrane curvature sensing of the lipid-anchored K-Ras small GTPase JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.201900343 VL - 2 IS - 4 SP - e201900343 AU - Hong Liang AU - Huanwen Mu AU - Frantz Jean-Francois AU - Bindu Lakshman AU - Suparna Sarkar-Banerjee AU - Yinyin Zhuang AU - Yongpeng Zeng AU - Weibo Gao AU - Ana Maria Zaske AU - Dwight V Nissley AU - Alemayehu A Gorfe AU - Wenting Zhao AU - Yong Zhou Y1 - 2019/08/01 UR - https://www.life-science-alliance.org/content/2/4/e201900343.abstract N2 - 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-RasG12V 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-RasG12V PM curvature sensing. In cells and synthetic bilayers, only mixed-chain PS species, but not other PS species tested, mediate K-RasG12V membrane curvature sensing. Thus, K-Ras nanoclusters act as relay stations to convert mechanical perturbations to mitogenic signaling. ER -