title: Palmitoylated Ras proteins traffic through recycling endosomes to the plasma membrane during exocytosis.
abstract: Ras proteins regulate cell growth, death, and differentiation, and it is well established that this functional versatility is accomplished through their different subcellular localizations. Palmitoylated H- and N-Ras are believed to localize at the perinuclear Golgi and plasma membrane (PM). Notably, however, recycling endosomes (REs) also localize to a perinuclear region, which is often indistinguishable from the Golgi. In this study, we show that active palmitoylated Ras proteins mainly localize intracellularly at REs and that REs act as a way station along the post-Golgi exocytic pathway to the PM. H-Ras requires two palmitoyl groups for RE targeting. The lack of either or both palmitoyl groups leads to the mislocalization of the mutant proteins to the endoplasmic reticulum, Golgi apparatus, or the PM. Therefore, we demonstrate that palmitoylation directs Ras proteins to the correct intracellular organelles for trafficking and activity.
authors.affiliation: Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
authors.forename: Ryo
authors.initials: R
authors.lastname: Misaki
authors.forename: Miki
authors.initials: M
authors.lastname: Morimatsu
authors.forename: Takefumi
authors.initials: T
authors.lastname: Uemura
authors.forename: Satoshi
authors.initials: S
authors.lastname: Waguri
authors.forename: Eiji
authors.initials: E
authors.lastname: Miyoshi
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Taniguchi
authors.forename: Michiyuki
authors.initials: M
authors.lastname: Matsuda
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Taguchi
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D019556:COS Cells; D002462:Cell Membrane / Q000378:metabolism*; D002522:Chlorocebus aethiops; D004721:Endoplasmic Reticulum / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism*; D005089:Exocytosis; D006056:Golgi Apparatus / Q000378:metabolism; D054878:Lipoylation; D008969:Molecular Sequence Data; D021382:Protein Sorting Signals; D021381:Protein Transport; D018631:ras Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D021382:Protein Sorting Signals; D018631:ras Proteins