NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane

• DOI: 10.26508/lsa.202000972
• Publication Date: 2021-02-12T15:44:50Z
• Authors: Ian M Ahearn; Helen R Court; Farid Siddiqui; Daniel Abankwa; Mark R Philips
• Keywords: Palmitoylation; Transport protein

Isoprenylcysteine carboxyl methyltransferase (ICMT) is the third of three enzymes that sequentially modify C-terminus CaaX proteins, including RAS. Although all four RAS proteins are substrates for ICMT, each traffics to membranes differently by virtue their hypervariable regions differentially palmitoylated. We found among NRAS was unique in requiring ICMT delivery PM, a consequence having only single palmitoylation site as its secondary affinity module. not absolutely required palmitoylation, acylation diminished absence ICMT. Photoactivation and FRAP GFP-NRAS revealed increase flux at Golgi, independent Association with prenyl-protein chaperone PDE6δ also promoted anterograde trafficking from Golgi. conclude methylation efficient binding, homeostatic through processes direct plasma membrane.