Palmitoylated Ras proteins traffic through recycling endosomes to the plasma membrane during exocytosis.
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.
Misaki
Ryo
R
Institute for Molecular Bioscience, University of Queensland, Brisbane, Queensland 4072, Australia.
Morimatsu
Miki
M
Uemura
Takefumi
T
Waguri
Satoshi
S
Miyoshi
Eiji
E
Taniguchi
Naoyuki
N
Matsuda
Michiyuki
M
Taguchi
Tomohiko
T
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*
D021382:Protein Sorting Signals; D018631:ras Proteins