Rasosomes originate from the Golgi to dispense Ras signals

A. Grunwald, I. Gottfried, A. D. Cox, R. Haklai, Y. Kloog*, U. Ashery

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Ras proteins undergo an incompletely understood trafficking process in the cell. Rasosomes are protein nanoparticles of 80100 nm diameter that carry lipidated Ras isoforms (H-Ras and N-Ras) as well as their effectors through the cytoplasm and near the plasma membrane (PM). In this study, we identified the subcellular origin of rasosomes and how they spread Ras proteins through the cell. We found no dependency of rasosome formation on galectins, or on the GDP-/GTP-bound state of Ras. We found that significantly more rasosomes are associated with forms of Ras that are localized to the Golgi, namely N-Ras or the singly palmitoylated H-Ras mutant (C181S). To explore the possibility that rasosome originate from the Golgi, we used photoactivatable (PA)-GFP-H-Ras mutants and showed that rasosomes bud from the Golgi in a two-step mechanism. Newly released rasosomes first move in an energy-dependent directed fashion and then convert to randomly diffusing rasosomes. Dual fluorescence time-lapse imaging revealed the appearance of dually labeled rasosomes, indicating a dynamic exchange of cytoplasmic and PM-associated Ras with rasosome-associated Ras. Finally, higher levels of rasosomes correlate with higher levels of ERK phosphorylation, a key marker of Ras downstream signaling. We suggest that H-Ras and N-Ras proteins exchange with rasosomes that can function as carriers of palmitoylated Ras and its signals.

Original languageEnglish
JournalCell Death and Disease
Volume4
Issue number2
DOIs
StatePublished - Feb 2013

Funding

FundersFunder number
Prajs-Drimmer Institute for the Development of Anti-Degenerative Drugs
United States-Israel Binational Science Foundation2009279
Israel Science Foundation912/06, 1211/07
Tel Aviv University

    Keywords

    • Brownian motion
    • Golgi budding
    • Rasosomes
    • Signaling
    • Trafficking

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