Figure 1.

Specific lipids within RAS nanoclusters directly participate in effector recruitment. RAS nanoclusters possess distinct lipid profiles. The specific lipids enriched within these nanoclusters not only contribute to the structural integrity of the nanoclusters, but also directly participate in effector recruitment. Most RAS effectors contain specific lipid-binding domains. For example, RAF, a major KRAS effector, possesses separate PS- and PA-binding domains. Efficient recruitment of RAF to the PM, a key step in the activation of RAF, requires synergistic binding to both the GTP-bound active KRAS and specific lipids including PS and PA.