title: The redox sensor TXNL1 plays a regulatory role in fluid phase endocytosis.
abstract: BACKGROUND
  Small GTPases of the Rab family can cycle between a GTP- and a GDP-bound state and also between membrane and cytosol. The latter cycle is mediated by the Guanine Nucleotide Dissociation Inhibitor GDI, which can selectively extract GDP-bound Rab proteins from donor membranes, and then reload them on target membranes. In previous studies, we found that capture of the small GTPase Rab5, a key regulator of endocytic membrane traffic, by GDI is stimulated by oxidative stress via p38MAPK, resulting in increased fluid phase endocytosis.
  
  
  RESULTS
  When purifying the GDI stimulating activity we found that that it copurified with a high MW protein complex, which included p38MAPK. Here we report the identification and characterization of another component of this complex as the thioredoxin-like protein TXNL1. Our observations indicate that TXNL1 play a selective role in the regulation of fluid phase endocytosis, by controlling GDI capacity to capture Rab5.
  
  
  CONCLUSIONS
  Oxidants, which are known to cause cellular damage, can also trigger signaling pathways, in particular via members of the thioredoxin family. We propose that TXNL1 acts as an effector of oxidants or a redox sensor by converting redox changes into changes of GDI capacity to capture Rab5, which in turn modulates fluid phase endocytosis.
authors.affiliation: Department of Biochemistry, University of Geneva, Geneva, Switzerland.
authors.forename: Michela
authors.initials: M
authors.lastname: Felberbaum-Corti
authors.forename: Etienne
authors.initials: E
authors.lastname: Morel
authors.forename: Valeria
authors.initials: V
authors.lastname: Cavalli
authors.forename: Francis
authors.initials: F
authors.lastname: Vilbois
authors.forename: Jean
authors.initials: J
authors.lastname: Gruenberg
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D006224:Cricetinae; D004705:Endocytosis / Q000502:physiology*; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism; D006801:Humans; D008969:Molecular Sequence Data; D010084:Oxidation-Reduction; D051381:Rats; D013879:Thioredoxins / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
chemical_list: D020730:Guanine Nucleotide Dissociation Inhibitors; C504766:TXNL1 protein, human; C504765:Txnl1 protein, rat; D013879:Thioredoxins; D048051:p38 Mitogen-Activated Protein Kinases; D020696:rab5 GTP-Binding Proteins