Developmental control of endocytosis in dendritic cells by Cdc42.
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.
Garrett
W S
WS
Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Chen
L M
LM
Kroschewski
R
R
Ebersold
M
M
Turley
S
S
Trombetta
S
S
Galán
J E
JE
Mellman
I
I
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*
D001426:Bacterial Proteins; D001427:Bacterial Toxins; D002966:Clathrin; C031815:toxB protein, Clostridium difficile; D020764:cdc42 GTP-Binding Protein