title: The differential palmitoylation states of N-Ras and H-Ras determine their distinct Golgi subcompartment localizations.
abstract: Despite a high degree of structural homology and shared exchange factors, effectors and GTPase activating proteins, a large body of evidence suggests functional heterogeneity among Ras isoforms. One aspect of Ras biology that may explain this heterogeneity is the differential subcellular localizations driven by the C-terminal hypervariable regions of Ras proteins. Spatial heterogeneity has been documented at the level of organelles: palmitoylated Ras isoforms (H-Ras and N-Ras) localize on the Golgi apparatus whereas K-Ras4B does not. We tested the hypothesis that spatial heterogeneity also exists at the sub-organelle level by studying the localization of differentially palmitoylated Ras isoforms within the Golgi apparatus. Using confocal, live-cell fluorescent imaging and immunogold electron microscopy we found that, whereas the doubly palmitoylated H-Ras is distributed throughout the Golgi stacks, the singly palmitoylated N-Ras is polarized with a relative paucity of expression on the trans Golgi. Using palmitoylation mutants, we show that the different sub-Golgi distributions of the Ras proteins are a consequence of their differential degree of palmitoylation. Thus, the acylation state of Ras proteins controls not only their distribution between the Golgi apparatus and the plasma membrane, but also their distribution within the Golgi stacks.
authors.affiliation: Department of Pathology, New York University School of Medicine, New York, New York.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Lynch
authors.forename: Harriet
authors.initials: H
authors.lastname: Snitkin
authors.forename: Iwona
authors.initials: I
authors.lastname: Gumper
authors.forename: Mark R
authors.initials: MR
authors.lastname: Philips
authors.forename: David
authors.initials: D
authors.lastname: Sabatini
authors.forename: Angel
authors.initials: A
authors.lastname: Pellicer
mesh_terms: D002451:Cell Compartmentation / Q000235:genetics*; D002460:Cell Line; D011905:Genes, ras; D006056:Golgi Apparatus / Q000235:genetics / Q000648:ultrastructure*; D006801:Humans; D054878:Lipoylation / Q000235:genetics; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D015398:Signal Transduction; D018631:ras Proteins / Q000235:genetics* / Q000648:ultrastructure
chemical_list: D020033:Protein Isoforms; D018631:ras Proteins