title: Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells.
abstract: Cell division cycle 42 (Cdc42) is a member of the Rho guanosine triphosphatase family and has pivotal functions in actin organization, cell migration, and proliferation. To further study the molecular mechanisms of dendritic cell (DC) regulation by Cdc42, we used Cdc42-deficient DCs. Cdc42 deficiency renders DCs phenotypically mature as they up-regulate the co-stimulatory molecule CD86 from intracellular storages to the cell surface. Cdc42 knockout DCs also accumulate high amounts of invariant chain-major histocompatibility complex (MHC) class II complexes at the cell surface, which cannot efficiently present peptide antigens (Ag's) for priming of Ag-specific CD4 T cells. Proteome analyses showed a significant reduction in lysosomal MHC class II-processing proteins, such as cathepsins, which are lost from DCs by enhanced secretion. As these effects on DCs can be mimicked by chemical actin disruption, our results propose that Cdc42 control of actin dynamics keeps DCs in an immature state, and cessation of Cdc42 activity during DC maturation facilitates secretion as well as rapid up-regulation of intracellular molecules to the cell surface.
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Schulz
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Stutte
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, 81377 Munich, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Hogl
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Nancy
authors.initials: N
authors.lastname: Luckashenak
authors.affiliation: Department of Dermatology, University Hospital of Erlangen, 91052 Erlangen, Germany.
authors.forename: Diana
authors.initials: D
authors.lastname: Dudziak
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Céline
authors.initials: C
authors.lastname: Leroy
authors.affiliation: Adolf Butenandt Institute, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Ignasi
authors.initials: I
authors.lastname: Forné
authors.affiliation: Adolf Butenandt Institute, Ludwig Maximilians University Munich, 80336 Munich, Germany.
authors.forename: Axel
authors.initials: A
authors.lastname: Imhof
authors.affiliation: Deutsches Zentrum für Neurodegenerative Erkrankungen, 81377 Munich, Germany.
authors.forename: Stephan A
authors.initials: SA
authors.lastname: Müller
authors.affiliation: Molecular Pathology Section, Biotech Research and Innovation Center, University of Copenhagen, 2200 Copenhagen, Denmark.
authors.forename: Cord H
authors.initials: CH
authors.lastname: Brakebusch
authors.affiliation: Munich Cluster for Systems Neurology, Ludwig Maximilians University Munich, 80336 Munich, Germany Deutsches Zentrum für Neurodegenerative Erkrankungen, 81377 Munich, Germany Neuroproteomics, Klinikum rechts der Isar, Institute for Advanced Study, Technische Universität München, 80333 Munich, Germany.
authors.forename: Stefan F
authors.initials: SF
authors.lastname: Lichtenthaler
authors.affiliation: Institute for Immunology, Ludwig Maximilians University Munich, 80336 Munich, Germany brocker@lmu.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Brocker
mesh_terms: D000199:Actins / Q000276:immunology / Q000378:metabolism*; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D051940:B7-2 Antigen / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D002403:Cathepsins / Q000378:metabolism; D002462:Cell Membrane / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D044783:F-Box Proteins / Q000276:immunology / Q000378:metabolism*; D000073979:F-Box-WD Repeat-Containing Protein 7; D005802:Genes, MHC Class II / Q000276:immunology; D008247:Lysosomes / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D044767:Ubiquitin-Protein Ligases / Q000276:immunology / Q000378:metabolism*; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000199:Actins; D051940:B7-2 Antigen; D044783:F-Box Proteins; D000073979:F-Box-WD Repeat-Containing Protein 7; C513272:Fbxw7 protein, mouse; D044767:Ubiquitin-Protein Ligases; D002403:Cathepsins