The redox sensor TXNL1 plays a regulatory role in fluid phase endocytosis.
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.
Felberbaum-Corti
Michela
M
Department of Biochemistry, University of Geneva, Geneva, Switzerland.
Morel
Etienne
E
Cavalli
Valeria
V
Vilbois
Francis
F
Gruenberg
Jean
J
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
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