Proteomics

Dataset Information

66

Cdc42 controls DC-maturation


ABSTRACT: Cell division cycle 42 (Cdc42) is a member of the Rho GTPase family and has pivotal functions in actin organization, cell migration and proliferation. Cdc42 has been shown to regulate antigen (Ag)-uptake in immature dendritic cells (DC) and controls their migration from tissues to lymph nodes. Previous reports demonstrated that Cdc42 is inactivated upon DC-maturation to avoid continued Ag-acquisition. To further study the molecular mechanisms of DC-control by Cdc42, we used bone marrow-derived DCs from Cdc42-deficient mice. We show that Cdc42-deficient DCs are phenotypically mature without additional maturation stimuli, as they upregulate CD86 from intracellular storages to the cell surface. They also accumulate invariant chain (Ii)-MHC class II complexes at the cell surface, which cannot efficiently present peptide Ag for priming of Ag-specific CD4 T cells. Lack of Cdc42 in immature DCs does not allow MHC class II maturation, as lysosomal Cathepsins are lost into the supernatant and Ii-MHC class II complexes cannot mature. Therefore Cdc42-deficient DCs are "pseudomature" and lose most functional hallmarks of antigen-presenting cells. Our results propose that Cdc42 keeps DCs in an immature state, while downregulation of Cdc42-activity during maturation facilitates generation of CD86+MHCII+ mature DCs.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Mus musculus  

TISSUE(S): Dendritic Cell

DISEASE(S): Not Available

SUBMITTER: Stephan Mueller  

LAB HEAD: Thomas Brocker

PROVIDER: PXD001934 | Pride | 2015-10-12

REPOSITORIES: Pride

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Publications

Cdc42-dependent actin dynamics controls maturation and secretory activity of dendritic cells.

Schulz Anna M AM   Stutte Susanne S   Hogl Sebastian S   Luckashenak Nancy N   Dudziak Diana D   Leroy Céline C   Forné Ignasi I   Imhof Axel A   Müller Stephan A SA   Brakebusch Cord H CH   Lichtenthaler Stefan F SF   Brocker Thomas T  

The Journal of cell biology 20151101 3


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 c  ...[more]

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