Article (Scientific journals)
NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane
Ahearn, Ian M.; Court, Helen R.; Siddiqui, Farid et al.
2021In Life Science Alliance
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Keywords :
RAS; Isoprenylcysteine carboxyl methyltransferase (ICMT); Trafficking
Abstract :
[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.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
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  ;  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
External co-authors :
yes
Language :
English
Title :
NRAS is unique among RAS proteins in requiring ICMT for trafficking to the plasma membrane
Publication date :
12 February 2021
Journal title :
Life Science Alliance
ISSN :
2575-1077
Publisher :
Life Science Alliance (LLC), Woodbury, United States
Peer reviewed :
Peer Reviewed verified by ORBi
Focus Area :
Systems Biomedicine
Available on ORBilu :
since 22 March 2021

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