title: Transport to Rhebpress activity.
abstract: The small GTPases from the rat sarcoma (Ras) superfamily are a heterogeneous group of proteins of about 21 kDa that act as molecular switches, modulating cell signaling pathways and controlling diverse cellular processes. They are active when bound to guanosine triphosphate (GTP) and inactive when bound to guanosine diphosphate (GDP). Ras homolog enriched in brain (Rheb) is a member of the Ras GTPase superfamily and a key activator of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). We recently determined that microspherule protein 1 (MCRS1) maintains Rheb at lysosomal surfaces in an amino acid-dependent manner. MCRS1 depletion promotes the formation of the GDP-bound form of Rheb, which is then delocalized from the lysosomal platform and transported to endocytic recycling vesicles, leading to mTORC1 inactivation. During this delocalization process, Rheb-GDP remains farnesylated and associated with cellular endomembranes. These findings provide new insights into the regulation of small GTPases, whose activity depends on both their GTP/GDP switch state and their capacity to move between different cellular membrane-bound compartments. Dynamic spatial transport between compartments makes it possible to alter the proximity of small GTPases to their activatory sites depending on the prevailing physiological and cellular conditions.
authors.affiliation: a Cancer Cell Biology Program, Growth Factors, Nutrients and Cancer Group , Centro Nacional de Investigaciones Oncológicas , CNIO , Madrid , Spain.
authors.forename: Amanda
authors.initials: A
authors.lastname: Garrido
authors.affiliation: a Cancer Cell Biology Program, Growth Factors, Nutrients and Cancer Group , Centro Nacional de Investigaciones Oncológicas , CNIO , Madrid , Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Brandt
authors.affiliation: a Cancer Cell Biology Program, Growth Factors, Nutrients and Cancer Group , Centro Nacional de Investigaciones Oncológicas , CNIO , Madrid , Spain.
authors.forename: Nabil
authors.initials: N
authors.lastname: Djouder
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002462:Cell Membrane / Q000378:metabolism; D004789:Enzyme Activation; D006153:Guanosine Diphosphate / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000378:metabolism*; D008247:Lysosomes / Q000378:metabolism; D020559:Monomeric GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D021381:Protein Transport; D051381:Rats
chemical_list: D009687:Nuclear Proteins; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D020559:Monomeric GTP-Binding Proteins
keywords: MCRS1; Ras superfamily; Rheb; TSC2; amino acids; mTORC1; small GTPases; vesicle transport