A1 Refereed original research article in a scientific journal

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




AuthorsAhearn Ian M., Court Helen R., Siddiqui Farid, Abankwa Daniel, Philips Mark R.

PublisherRockefeller University Press

Publication year2021

JournalLife Science Alliance

Journal name in sourceLife Science Alliance

Volume4

Issue5

ISSN2575-1077

eISSN2575-1077

DOIhttps://doi.org/10.26508/LSA.202000972

Self-archived copy’s web addresshttps://research.utu.fi/converis/portal/Publication/54103623


Abstract

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


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Last updated on 2024-26-11 at 22:56