PMID- 10975523 OWN - NLM STAT- MEDLINE DCOM- 20000919 LR - 20190705 IS - 0092-8674 (Print) IS - 0092-8674 (Linking) VI - 102 IP - 3 DP - 2000 Aug 4 TI - Developmental control of endocytosis in dendritic cells by Cdc42. PG - 325-34 AB - 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. FAU - Garrett, W S AU - Garrett WS AD - Department of Cell Biology, Ludwig Institute for Cancer Research, Yale University School of Medicine, New Haven, Connecticut 06520, USA. FAU - Chen, L M AU - Chen LM FAU - Kroschewski, R AU - Kroschewski R FAU - Ebersold, M AU - Ebersold M FAU - Turley, S AU - Turley S FAU - Trombetta, S AU - Trombetta S FAU - Galan, J E AU - Galan JE FAU - Mellman, I AU - Mellman I LA - eng GR - AI-34098/AI/NIAID NIH HHS/United States GR - CA-46128/CA/NCI NIH HHS/United States GR - GM-29765/GM/NIGMS NIH HHS/United States GR - etc. PT - Journal Article PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Cell JT - Cell JID - 0413066 RN - 0 (Bacterial Proteins) RN - 0 (Bacterial Toxins) RN - 0 (Clathrin) RN - 0 (toxB protein, Clostridium difficile) RN - EC 3.6.5.2 (cdc42 GTP-Binding Protein) SB - IM MH - Animals MH - *Antigen Presentation MH - *Bacterial Proteins MH - Bacterial Toxins/pharmacology MH - Cell Differentiation MH - Clathrin MH - Coated Pits, Cell-Membrane MH - Dendritic Cells/*immunology MH - Down-Regulation MH - *Endocytosis MH - Enzyme Activation MH - Male MH - Mice MH - Pinocytosis MH - Salmonella typhimurium/immunology MH - cdc42 GTP-Binding Protein/antagonists & inhibitors/*metabolism EDAT- 2000/09/07 11:00 MHDA- 2000/09/23 11:01 CRDT- 2000/09/07 11:00 PHST- 2000/09/07 11:00 [pubmed] PHST- 2000/09/23 11:01 [medline] PHST- 2000/09/07 11:00 [entrez] AID - S0092-8674(00)00038-6 [pii] AID - 10.1016/s0092-8674(00)00038-6 [doi] PST - ppublish SO - Cell. 2000 Aug 4;102(3):325-34. doi: 10.1016/s0092-8674(00)00038-6.