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Title: Membrane curvature sensing of the lipid-anchored K-Ras small GTPase
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
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.
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
Fulltext Permission: open
Fulltext Availability: With Fulltext
Appears in Collections:SCBE Journal Articles

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