title: Ras moves to stay in place.
abstract: Ras is a major intracellular signaling hub. This elevated position comes at a precarious cost: a single point mutation can cause aberrant signaling. The capacity of Ras for signaling is inextricably linked to its enrichment at the plasma membrane (PM). This PM localization is dynamically maintained by three essential elements: alteration of membrane affinities via lipidation and membrane-interaction motifs; trapping on specific membranes coupled with unidirectional vesicular transport to the PM; and regulation of diffusion via interaction with a solubilization factor. This system constitutes a cycle that primarily corrects for the entropic equilibration of Ras to all membranes that dilutes its signaling capacity. We illuminate how this reaction-diffusion system maintains an out-of-equilibrium localization of Ras GTPases and thereby confers signaling functionality to the PM.
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Malte
authors.initials: M
authors.lastname: Schmick
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany.
authors.forename: Astrid
authors.initials: A
authors.lastname: Kraemer
authors.affiliation: Department of Systemic Cell Biology, Max Planck Institute of Molecular Physiology, Otto-Hahn-Strasse 11, 44227 Dortmund, Germany; Faculty of Chemistry and Chemical Biology, TU Dortmund, Otto-Hahn-Strasse 6, 44227 Dortmund, Germany. Electronic address: philippe.bastiaens@mpi-dortmund.mpg.de.
authors.forename: Philippe I H
authors.initials: PI
authors.lastname: Bastiaens
mesh_terms: D002462:Cell Membrane / Q000502:physiology*; D006801:Humans; D009154:Mutation; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D015398:Signal Transduction; D018631:ras Proteins / Q000502:physiology*
chemical_list: D018631:ras Proteins
keywords: PDEδ–Arl2 delivery system; Ras localization; Ras signaling; recycling endosome; spatial cycles