Developmental control of endocytosis in dendritic cells by Cdc42

Cell. 2000 Aug 4;102(3):325-34. doi: 10.1016/s0092-8674(00)00038-6.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigen Presentation*
  • Bacterial Proteins*
  • Bacterial Toxins / pharmacology
  • Cell Differentiation
  • Clathrin
  • Coated Pits, Cell-Membrane
  • Dendritic Cells / immunology*
  • Down-Regulation
  • Endocytosis*
  • Enzyme Activation
  • Male
  • Mice
  • Pinocytosis
  • Salmonella typhimurium / immunology
  • cdc42 GTP-Binding Protein / antagonists & inhibitors
  • cdc42 GTP-Binding Protein / metabolism*


  • Bacterial Proteins
  • Bacterial Toxins
  • Clathrin
  • toxB protein, Clostridium difficile
  • cdc42 GTP-Binding Protein