Developmental control of endocytosis in dendritic cells by Cdc42

Dendritic cells (DCs) developmentally regulate antigen uptake by controllin g their endocytic capacity. Immature DCs actively internalize antigen. Howe ver, mature DCs are poorly endocytic, functioning instead to present antige ns to T cells. We have found that endocytic downregulation reflects a decre ase in endocytic activity controlled by Rho family GTPases, especially Cdc4 2. Blocking Cdc42 function by Toxin B treatment or injection of dominant-ne gative inhibitors of Cdc42 abrogates endocytosis in immature DCs. In mature DCs, injection of constitutively active Cdc42 or microbial delivery of a C dc42 nucleotide exchange factor reactivates endocytosis. DCs regulate endog enous levels of Cdc42-GTP with activated Cdc42 detectable only in immature cells. We conclude that DCs developmentally regulate endocytosis at least i n part by controlling levels of activated Cdc42.