@article{d0f6f5fc44274a669f1203aa51676bb0,
title = "Rasosomes originate from the Golgi to dispense Ras signals",
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.",
keywords = "Brownian motion, Golgi budding, Rasosomes, Signaling, Trafficking",
author = "A. Grunwald and I. Gottfried and Cox, {A. D.} and R. Haklai and Y. Kloog and U. Ashery",
note = "Funding Information: Acknowledgements. This work was supported by Grant 2005344 from the United States-Israel Binational Science Foundation (Y. Kloog and A.D. Cox), by the Israel Science Foundation (Grant no. 912/06 to Y.K. and U.A.; Grant no. 1211/07 to U.A.), the BSF (Grant no. 2009279 to U.A.) and by the Prajs-Drimmer Institute for The Development of Anti-degenerative Drugs (Y. Kloog) and by the Tel Aviv University Center for Nanoscience and Nanotechnology (I.G.). Y. Kloog is an incumbent of The Jack H. Skirball Chair in Applied Neurobiology.",
year = "2013",
month = feb,
doi = "10.1038/cddis.2013.16",
language = "אנגלית",
volume = "4",
journal = "Cell Death and Disease",
issn = "2041-4889",
publisher = "Nature Publishing Group",
number = "2",
}