Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters

Zhou, Yong, Liang, Hong, Rodkey, Travis, Ariotti, Nicholas, Parton, Robert G. and Hancock, John F. (2013) Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters. Molecular and Cellular Biology, 34 5: 862-876. doi:10.1128/MCB.01227-13

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Author Zhou, Yong
Liang, Hong
Rodkey, Travis
Ariotti, Nicholas
Parton, Robert G.
Hancock, John F.
Title Signal integration by lipid-mediated spatial cross talk between Ras nanoclusters
Journal name Molecular and Cellular Biology   Check publisher's open access policy
ISSN 0270-7306
Publication date 2013-12-23
Year available 2013
Sub-type Article (original research)
DOI 10.1128/MCB.01227-13
Open Access Status File (Publisher version)
Volume 34
Issue 5
Start page 862
End page 876
Total pages 15
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Language eng
Abstract Lipid-anchored Ras GTPases form transient, spatially segregated nanoclusters on the plasma membrane that are essential for high-fidelity signal transmission. The lipid composition of Ras nanoclusters however has not previously been investigated. High-resolution spatial mapping shows that different Ras nanoclusters have distinct lipid compositions indicating that Ras proteins engage in isoform-selective lipid sorting, and accounting for different signal outputs from each Ras isoform. Phosphatidylserine is a common constituent of all Ras nanoclusters but is only an obligate structural component of K-Ras nanoclusters. Segregation of K-Ras and H-Ras into spatially and compositionally distinct lipid assemblies is exquisitely sensitive to plasma membrane phosphatidylserine levels. Phosphatidylserine spatial organization is also modified by Ras nanocluster formation. In consequence Ras nanoclusters engage in remote lipid-mediated communication, whereby activated H-Ras disrupts the assembly and operation of spatially segregated K-Ras nanoclusters. Computational modeling and experiment reveal that complex effects of caveolin and cortical actin on Ras nanoclustering are similarly mediated through regulation of phosphatidylserine spatiotemporal dynamics. We conclude that phosphatidylserine maintains the lateral segregation of diverse lipid-based assemblies on the plasma membrane and that lateral connectivity between spatially remote lipid assemblies offers important, previously unexplored opportunities for signal integration and signal processing.
Keyword Ras proteins
Actin cytoskeleton
Phase separation
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID GM066717
Institutional Status UQ
Additional Notes Published online ahead of print 23 December 2013.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 37 times in Thomson Reuters Web of Science Article | Citations
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Created: Fri, 24 Jan 2014, 01:37:13 EST by Susan Allen on behalf of Institute for Molecular Bioscience