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|Title:||Membrane curvature sensing of the lipid-anchored K-Ras small GTPase||Authors:||Liang, Hong
Zaske, Ana Maria
Nissley, Dwight V.
Gorfe, Alemayehu A.
|Keywords:||Engineering::Bioengineering||Issue Date:||2019||Source:||Liang, H., Mu, H., Jean-Francois, F., Lakshman, B., Sarkar-Banerjee, S., Zhuang, Y., . . . Zhou, Y. (2019). Membrane curvature sensing of the lipid-anchored K-Ras small GTPase. Life Science Alliance, 2(4), e201900343-. doi:10.26508/lsa.201900343||Journal:||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.||URI:||https://hdl.handle.net/10356/141949||ISSN:||2575-1077||DOI:||10.26508/lsa.201900343||Rights:||© 2019 Liang et al. This article is available under a Creative Commons License (Attribution 4.0 International, as described at https://creativecommons.org/licenses/by/4.0/).||Fulltext Permission:||open||Fulltext Availability:||With Fulltext|
|Appears in Collections:||SCBE Journal Articles|
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