Membrane curvature sensing of the lipid-anchored K-Ras small GTPase

• Main Authors: Liang, Hong, Mu, Huanwen, Jean-Francois, Frantz, Lakshman, Bindu, Sarkar-Banerjee, Suparna, Zhuang, Yinyin, Zeng, Yongpeng, Gao, Weibo, Zaske, Ana Maria, Nissley, Dwight V., Gorfe, Alemayehu A., Zhao, Wenting, Zhou, Yong
• Other Authors: School of Chemical and Biomedical Engineering
• Format: Article
• Language: English
• Published: 2020
• Subjects: Engineering::Bioengineering; Plasma Membrane (PM) Curvature; GTPase
• Online Access: https://hdl.handle.net/10356/141949
• Institution: Nanyang Technological University

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.