@article {Liange201900343, author = {Hong Liang and Huanwen Mu and Frantz Jean-Francois and Bindu Lakshman and Suparna Sarkar-Banerjee and Yinyin Zhuang and Yongpeng Zeng and Weibo Gao and Ana Maria Zaske and Dwight V Nissley and Alemayehu A Gorfe and Wenting Zhao and Yong Zhou}, title = {Membrane curvature sensing of the lipid-anchored K-Ras small GTPase}, volume = {2}, number = {4}, elocation-id = {e201900343}, year = {2019}, doi = {10.26508/lsa.201900343}, publisher = {Life Science Alliance}, abstract = {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.}, URL = {https://www.life-science-alliance.org/content/2/4/e201900343}, eprint = {https://www.life-science-alliance.org/content/2/4/e201900343.full.pdf}, journal = {Life Science Alliance} }