Rasosomes originate from the Golgi to dispense Ras signals

Area of Science:

• Cell Biology
• Molecular Biology
• Protein Trafficking

Background:

• Ras proteins are crucial signaling molecules with incompletely understood cellular trafficking.
• Rasosomes, 80-100 nm nanoparticles, transport lipidated Ras isoforms (H-Ras, N-Ras) and effectors.

Purpose of the Study:

• To identify the subcellular origin of rasosomes.
• To elucidate the mechanism by which rasosomes spread Ras proteins.
• To investigate the functional significance of rasosomes in Ras signaling.

Main Methods:

• Utilized photoactivatable (PA)-GFP-H-Ras mutants to track rasosome formation.
• Employed dual fluorescence time-lapse imaging to observe Ras dynamics.
• Correlated rasosome levels with ERK phosphorylation as a signaling readout.

Main Results:

• Rasosome formation is independent of galectins and Ras GDP/GTP status.
• Rasosomes bud from the Golgi in a two-step process.
• Newly formed rasosomes exhibit directed movement followed by random diffusion.
• Evidence of dynamic exchange between cytoplasmic/PM-associated Ras and rasosome-associated Ras.
• Higher rasosome levels correlate with increased ERK phosphorylation.

Conclusions:

• Rasosomes originate from the Golgi and act as carriers for palmitoylated Ras isoforms.
• Rasosomes facilitate the transport and signaling of H-Ras and N-Ras.
• Rasosome dynamics involve directed transport and random diffusion, with active Ras exchange.