Reference : NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane
Scientific journals : Article
Life sciences : Biochemistry, biophysics & molecular biology
Systems Biomedicine
http://hdl.handle.net/10993/46652
NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane
English
Ahearn, Ian M. [New York University Grossman School of Medicine, New York, USA > The Ronald O Perelman Department of Dermatology > > ; New York University Langone Medical Center, New York, USA. > The Perlmutter Cancer Center > > ; Veterans Affairs New York Harbor Healthcare System, Manhattan Campus, New York, USA]
Court, Helen R. [New York University Langone Medical Center, New York, USA > The Perlmutter Cancer Center]
Siddiqui, Farid [University of Turku and Åbo Akademi University, Turku, Finland. > Turku Bioscience Centre]
Abankwa, Daniel mailto [University of Luxembourg > Faculty of Science, Technology and Medicine (FSTM) > Department of Life Sciences and Medicine (DLSM) > ; University of Turku and Åbo Akademi University, Turku, Finland. > Turku Bioscience Centre]
Philips, Mark R. [New York University Langone Medical Center, New York, USA > The Perlmutter Cancer Center]
12-Feb-2021
Life Science Alliance
Life Science Alliance (LLC)
Yes (verified by ORBilu)
International
2575-1077
Woodbury
United States
[en] RAS ; Isoprenylcysteine carboxyl methyltransferase (ICMT) ; Trafficking
[en] 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.
Researchers
http://hdl.handle.net/10993/46652
10.26508/lsa.202000972

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