Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling

Ariotti, Nicholas, Fernández-Rojo, Manuel, Zhou, Yong, Hill, Michelle M., Rodkey, Travis L., Inder, Kerry L., Tanner, Lukas B., Wenk, Markus R., Hancock, John F. and Parton, Robert G. (2014) Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling. Journal of Cell Biology, 204 5: 777-792. doi:10.1083/jcb.201307055

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Author Ariotti, Nicholas
Fernández-Rojo, Manuel
Zhou, Yong
Hill, Michelle M.
Rodkey, Travis L.
Inder, Kerry L.
Tanner, Lukas B.
Wenk, Markus R.
Hancock, John F.
Parton, Robert G.
Title Caveolae regulate the nanoscale organization of the plasma membrane to remotely control Ras signaling
Journal name Journal of Cell Biology   Check publisher's open access policy
ISSN 0021-9525
1540-8140
Publication date 2014-02-24
Sub-type Article (original research)
DOI 10.1083/jcb.201307055
Open Access Status File (Publisher version)
Volume 204
Issue 5
Start page 777
End page 792
Total pages 16
Place of publication New York, NY, United States
Publisher Rockefeller University Press
Language eng
Formatted abstract
The molecular mechanisms whereby caveolae exert control over cellular signaling have to date remained elusive. We have therefore explored the role caveolae play in modulating Ras signaling. Lipidomic and gene array analyses revealed that caveolin-1 (CAV1) deficiency results in altered cellular lipid composition, and plasma membrane (PM) phosphatidylserine distribution. These changes correlated with increased K-Ras expression and extensive isoform-specific perturbation of Ras spatial organization: in CAV1-deficient cells K-RasG12V nanoclustering and MAPK activation were enhanced, whereas GTP-dependent lateral segregation of H-Ras was abolished resulting in compromised signal output from H-RasG12V nanoclusters. These changes in Ras nanoclustering were phenocopied by the down-regulation of Cavin1, another crucial caveolar structural component, and by acute loss of caveolae in response to increased osmotic pressure. Thus, we postulate that caveolae remotely regulate Ras nanoclustering and signal transduction by controlling PM organization. Similarly, caveolae transduce mechanical stress into PM lipid alterations that, in turn, modulate Ras PM organization.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
UQ Diamantina Institute Publications
 
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Citation counts: TR Web of Science Citation Count  Cited 30 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 34 times in Scopus Article | Citations
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Created: Wed, 05 Mar 2014, 01:43:23 EST by Susan Allen on behalf of Institute for Molecular Bioscience