Comparative proteomic analysis of compartmentalised Ras signalling

Area of Science:

• Cellular Biology
• Molecular Signaling

Background:

• Ras proteins act as signaling hubs at the cell surface and within endomembrane compartments.
• The contribution of intracellular Ras pools to cell signaling remains an area of active investigation and debate.

Purpose of the Study:

• To investigate the global impact of compartmentalized Ras signaling on cellular processes.
• To determine the extent to which Ras proteins localized in different organelles influence downstream signaling pathways.

Main Methods:

• A global screen was employed to analyze compartmentalized Ras signaling.
• Protein abundance and phosphorylation levels were quantified across various cellular compartments.

Main Results:

• Ras localization to mitochondria or Golgi significantly altered protein abundance and phosphorylation.
• ER/Golgi- and endosomal-Ras showed weaker signaling outputs compared to mitochondrial or Golgi-localized Ras.
• ~80% of significantly changed phosphosites were modulated by organellar Ras signaling.
• Compartmentalized Ras signaling primarily influences gene expression, RNA splicing, and cell proliferation.

Conclusions:

• Compartmentalization critically influences Ras signaling outcomes.
• Endomembranous Ras signaling has widespread downstream effects on cellular functions.