title: Developmental control of endocytosis in dendritic cells by Cdc42.
abstract: Dendritic cells (DCs) developmentally regulate antigen uptake by controlling their endocytic capacity. Immature DCs actively internalize antigen. However, mature DCs are poorly endocytic, functioning instead to present antigens to T cells. We have found that endocytic downregulation reflects a decrease in endocytic activity controlled by Rho family GTPases, especially Cdc42. Blocking Cdc42 function by Toxin B treatment or injection of dominant-negative inhibitors of Cdc42 abrogates endocytosis in immature DCs. In mature DCs, injection of constitutively active Cdc42 or microbial delivery of a Cdc42 nucleotide exchange factor reactivates endocytosis. DCs regulate endogenous levels of Cdc42-GTP with activated Cdc42 detectable only in immature cells. We conclude that DCs developmentally regulate endocytosis at least in part by controlling levels of activated Cdc42.
authors.affiliation: Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: W S
authors.initials: WS
authors.lastname: Garrett
authors.forename: L M
authors.initials: LM
authors.lastname: Chen
authors.forename: R
authors.initials: R
authors.lastname: Kroschewski
authors.forename: M
authors.initials: M
authors.lastname: Ebersold
authors.forename: S
authors.initials: S
authors.lastname: Turley
authors.forename: S
authors.initials: S
authors.lastname: Trombetta
authors.forename: J E
authors.initials: JE
authors.lastname: Galán
authors.forename: I
authors.initials: I
authors.lastname: Mellman
mesh_terms: D000818:Animals; D017951:Antigen Presentation; D001426:Bacterial Proteins; D001427:Bacterial Toxins / Q000494:pharmacology; D002454:Cell Differentiation; D002966:Clathrin; D003034:Coated Pits, Cell-Membrane; D003713:Dendritic Cells / Q000276:immunology*; D015536:Down-Regulation; D004705:Endocytosis; D004789:Enzyme Activation; D008297:Male; D051379:Mice; D010873:Pinocytosis; D012486:Salmonella typhimurium / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002966:Clathrin; C031815:toxB protein, Clostridium difficile; D020764:cdc42 GTP-Binding Protein