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

2015 ◽  
Vol 211 (3) ◽  
pp. 553-567 ◽  
Author(s):  
Anna M. Schulz ◽  
Susanne Stutte ◽  
Sebastian Hogl ◽  
Nancy Luckashenak ◽  
Diana Dudziak ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Molecular Mechanisms ◽  
Secretory Activity ◽  
Class Ii ◽  
Actin Dynamics ◽  
Actin Organization ◽  
Peptide Antigens ◽  
Enhanced Secretion ◽  
Guanosine Triphosphatase

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.

scholarly journals Lymphoid Tumors ofXenopus laeviswith Different Capacities for Growth in Larvae and Adults

1994 ◽  
Vol 3 (4) ◽  
pp. 297-307 ◽  
Author(s):  
Jacques Robert ◽  
Chantal Guiet ◽  
Louis Du Pasquier
Keyword(s):  
Cell Surface ◽  
Tumor Cell ◽  
Tumor Cells ◽  
Mhc Class I ◽  
Mhc Class Ii ◽  
Cell Lineage ◽  
Cell Types ◽  
Class Ii ◽  
Class I ◽  
Specific Marker

Three new lymphoid tumors offering an assortment of variants in terms of MHC class I expressions, MHC class II expression, and Ig gene transcription have been discovered in the amphibianXenopus. One was developed in an individual of the isogenic LG15 clone (LG15/0), one in a frog of the LG15/40 clone (derived from a small egg recombinant of LG15), and one (ff-2) in a maleffsib of the individual in which MAR1, the first lymphoid tumor in Xenopus was found 2 years ago. These tumors developed primarily as thymus outgrowths and were transplantable in histocompatible tadpoles but not in nonhistocompatible hosts. Whereas LG15/0 and LG15/40 tumor cells also grow in adult LG15 frogs, theff-2 tumor, like the MAR1 cell line, is rejected by adultffanimals. Using flow cytometry with fluorescence-labeled antibodies and immunoprecipitation analysis, we could demonstrate that, like MAR1, these three new tumors express on their cell surface lymphopoietic markers recognized by mAbs FIF6 and RC47, as well as T-cell lineage markers recognized by mAbs AM22 (CD8-1ike) and X21.2, but not by immunologobulin (Ig) nor MHC class II molecules. Another lymphocyte-specific marker AM15 is expressed by 15/0 and 15/40 but notff-2 tumor cells. Theff-2 tumor cell expresses MHC class molecule in association withβ2-microglobulin on the surface, 15/40 cells contain cytoplasmic Iαchain that is barely detected at the cell surface by fluocytometry, and 15/0 cells do not synthesize class Iαchain at all. The three new tumors all produce large amounts of IgM mRNA of two different sizes but no Ig protein on the membrane nor in the cytoplasm. All tumor cell types synthesize large amount of Myc mRNA and MHC class I-like transcripts considered to be non classical.

scholarly journals Modulation of Major Histocompatibility Class II Protein Expression by Varicella-Zoster Virus

2000 ◽  
Vol 74 (4) ◽  
pp. 1900-1907 ◽  
Author(s):  
Allison Abendroth ◽  
Barry Slobedman ◽  
Eunice Lee ◽  
Elizabeth Mellins ◽  
Mark Wallace ◽  
...  
Keyword(s):  
Cell Surface ◽  
Varicella Zoster Virus ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Northern Blot Hybridization ◽  
Major Histocompatibility ◽  
Varicella Zoster ◽  
Ifn Γ ◽  
In Cells

ABSTRACT We sought to investigate the effects of varicella-zoster virus (VZV) infection on gamma interferon (IFN-γ)-stimulated expression of cell surface major histocompatibility complex (MHC) class II molecules on human fibroblasts. IFN-γ treatment induced cell surface MHC class II expression on 60 to 86% of uninfected cells, compared to 20 to 30% of cells which had been infected with VZV prior to the addition of IFN-γ. In contrast, cells that were treated with IFN-γ before VZV infection had profiles of MHC class II expression similar to those of uninfected cell populations. Neither IFN-γ treatment nor VZV infection affected the expression of transferrin receptor (CD71). In situ and Northern blot hybridization of MHC II (MHC class II DR-α) RNA expression in response to IFN-γ stimulation revealed that MHC class II DR-α mRNA accumulated in uninfected cells but not in cells infected with VZV. When skin biopsies of varicella lesions were analyzed by in situ hybridization, MHC class II transcripts were detected in areas around lesions but not in cells that were infected with VZV. VZV infection inhibited the expression of Stat 1α and Jak2 proteins but had little effect on Jak1. Analysis of regulatory events in the IFN-γ signaling pathway showed that VZV infection inhibited transcription of interferon regulatory factor 1 and the MHC class II transactivator. This is the first report that VZV encodes an immunomodulatory function which directly interferes with the IFN-γ signal transduction via the Jak/Stat pathway and enables the virus to inhibit IFN-γ induction of cell surface MHC class II expression. This inhibition of MHC class II expression on VZV-infected cells in vivo may transiently protect cells from CD4+ T-cell immune surveillance, facilitating local virus replication and transmission during the first few days of cutaneous lesion formation.

From transcription to cell surface expression, the induction of MHC class II I-Aα by interferon-γ in macrophages is regulated at different levels

2001 ◽  
Vol 53 (2) ◽  
pp. 136-144 ◽  
Author(s):  
Martin Cullell-Young ◽  
Marta Barrachina ◽  
Carlos López-López ◽  
Eduard Goñalons ◽  
Jorge Lloberas ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Surface Expression ◽  
Class Ii ◽  
Interferon Γ ◽  
Cell Surface Expression ◽  
Different Levels

scholarly journals HIV-1 Nef promotes endocytosis of cell surface MHC class II molecules via a constitutive pathway

2009 ◽  
Vol 183 (11) ◽  
pp. 7611.1-7611
Author(s):  
A. Chaudhry ◽  
D. A. Verghese ◽  
S. R. Das ◽  
S. Jameel ◽  
A. George ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Hiv 1 ◽  
Mhc Class Ii Molecules

Lessons from the bare lymphocyte syndrome: molecular mechanisms regulating MHC class II expression

2000 ◽  
Vol 178 (1) ◽  
pp. 148-165 ◽  
Author(s):  
Jean-Marc Waldburger ◽  
Krzysztof Masternak ◽  
Annick Muhlethaler-Mottet ◽  
Jean Villard ◽  
Marie Peretti ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
Molecular Mechanisms ◽  
Class Ii ◽  
Bare Lymphocyte Syndrome

MHC Class II alpha/beta Heterodimeric Cell Surface Molecules Expressed from a Single Proviral Genome

1999 ◽  
Vol 10 (14) ◽  
pp. 2397-2405 ◽  
Author(s):  
Hideaki Shimada ◽  
Sharon Germana ◽  
Kai-Christian Sonntag ◽  
Papia Banerjee ◽  
Daniel Moore ◽  
...  
Keyword(s):  
Cell Surface ◽  
Mhc Class Ii ◽  
Class Ii ◽  
Cell Surface Molecules ◽  
Proviral Genome ◽  
Surface Molecules ◽  
Alpha Beta ◽  
Class Ii Alpha

scholarly journals The beta-tubulin isotype TUBB6 controls microtubule and actin dynamics in osteoclasts.

2021 ◽  
Author(s):  
Justine Maurin ◽  
Anne Morel ◽  
David Guérit ◽  
Julien Cau ◽  
Serge Urbach ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Actin Cytoskeleton ◽  
Molecular Mechanisms ◽  
Life Time ◽  
Negative Regulator ◽  
Actin Dynamics ◽  
Growth Speed ◽  
Actin Organization ◽  
Cytoskeleton Organization ◽  
Tubulin Isotype

Osteoclasts are bone resorbing cells that participate in the maintenance of bone health. Pathological increase in osteoclast activity causes bone loss eventually resulting in osteoporosis. Actin cytoskeleton of osteoclasts organizes into a belt of podosomes, which sustains the bone resorption apparatus and is maintained by microtubules. Better understanding of the molecular mechanisms regulating osteoclast cytoskeleton is key to understand the mechanisms of bone resorption, in particular to propose new strategies against osteoporosis. We reported recently that β-tubulin isotype TUBB6 is key for cytoskeleton organization in osteoclasts and for bone resorption. Here, using an osteoclast model CRISPR/Cas9 KO for Tubb6, we show that TUBB6 controls both microtubule and actin dynamics in osteoclasts. Osteoclasts KO for Tubb6 have reduced microtubule growth speed with longer growth life time, higher levels of acetylation and smaller EB1-caps. On the other hand, lack of TUBB6 increases podosome life time while the belt of podosomes is destabilized. Finally, we performed proteomic analyses of osteoclast microtubule-associated protein enriched fractions. This highlighted ARHGAP10 as a new microtubule-associated protein, which binding to microtubules appears to be negatively regulated by TUBB6. ARHGAP10 is a negative regulator of CDC42 activity, which participates in actin organization in osteoclasts. Our results suggest that TUBB6 plays a key role in the control of microtubule and actin cytoskeleton dynamics in osteoclasts. Moreover, by controlling ARHGAP10 association with microtubules, TUBB6 may participate in the local control CDC42 activity to ensure efficient bone resorption.

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