Membrane curvature sensing of the lipid-anchored K-Ras small GTPase.
Hong LiangHuanwen MuFrantz Jean-FrancoisBindu LakshmanSuparna Sarkar-BanerjeeYinyin ZhuangYongpeng ZengWeibo GaoAna Maria ZaskeDwight V NissleyAlemayehu A GorfeWenting ZhaoYong ZhouPublished in: Life science alliance (2019)
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.
Keyphrases
- induced apoptosis
- cell cycle arrest
- wild type
- signaling pathway
- air pollution
- cell death
- squamous cell carcinoma
- transcription factor
- oxidative stress
- cell therapy
- dendritic cells
- stem cells
- immune response
- single cell
- heavy metals
- fatty acid
- mesenchymal stem cells
- young adults
- risk assessment
- bone marrow
- molecular dynamics simulations
- papillary thyroid
- squamous cell