374 research outputs found
CCR2 acts as scavenger for CCL2 during monocyte chemotaxis.
No full textBackgroundLeukocyte migration is essential for effective host defense against invading pathogens and during immune homeostasis. A hallmark of the regulation of this process is the presentation of chemokines in gradients stimulating leukocyte chemotaxis via cognate chemokine receptors. For efficient migration, receptor responsiveness must be maintained whilst the cells crawl on cell surfaces or on matrices along the attracting gradient towards increasing concentrations of agonist. On the other hand agonist-induced desensitization and internalization is a general paradigm for chemokine receptors which is inconsistent with the prolonged migratory capacity.Methodology/principal findingsChemotaxis of monocytes was monitored in response to fluorescent CCL2-mCherry by time-lapse video microscopy. Uptake of the fluorescent agonist was used as indirect measure to follow the endogenous receptor CCR2 expressed on primary human monocytes. During chemotaxis CCL2-mCherry becomes endocytosed as cargo of CCR2, however, the internalization of CCR2 is not accompanied by reduced responsiveness of the cells due to desensitization.Conclusions/significanceDuring chemotaxis CCR2 expressed on monocytes internalizes with the bound chemoattractant, but cycles rapidly back to the plasma membrane to maintain high responsiveness. Moreover, following relocation of the source of attractant, monocytes can rapidly reverse their polarization axis organizing a new leading edge along the newly formed gradient, suggesting a uniform distribution of highly receptive CCR2 on the plasma membrane. The present observations further indicate that during chemotaxis CCR2 acts as scavenger consuming the chemokine forming the attracting cue
Albert Vigoleis Thelen: ecos literários de um exílio em Portugal
No full textCom uma obra que se relaciona intimamente com a sua biografia, Albert Vigoleis Thelen foi um autor em contracorrente. Após alguns apontamentos sobre a sua vida de errância e as particularidades narrativas que mais o distinguiram, centrar-me-ei no eco literário do seu exílio em Portugal.With a work closely related to his biography, Albert Vigoleis Thelen was an author in countercurrent. After a few notes on his life of wandering and the narrative characteristics that most distinguished him, the A. will focus on literary echoes of his exile in Portugal
How chemokines invite leukocytes to dance
No full textA prominent activity of the chemokine system is the regulation of leukocyte trafficking. Here we summarize recent findings on the initial steps in chemokine receptor-induced signal transduction in leukocytes. In particular, we discuss the potential influences of the formation of oligomers of ligand and receptor and of coupling between chemokine signals and regulators of the cytoskeleton, such as small GTPases
ACKR3 expression on diffuse large B cell lymphoma is required for tumor spreading and tissue infiltration
No full textLeukocyte Tracking Database, a collection of immune cell tracks from intravital 2-photon microscopy videos.
No full textRecent advances in intravital video microscopy have allowed the visualization of leukocyte behavior in vivo, revealing unprecedented spatiotemporal dynamics of immune cell interaction. However, state-of-the-art software and methods for automatically measuring cell migration exhibit limitations in tracking the position of leukocytes over time. Challenges arise both from the complex migration patterns of these cells and from the experimental artifacts introduced during image acquisition. Additionally, the development of novel tracking tools is hampered by the lack of a sound ground truth for algorithm validation and benchmarking. Therefore, the objective of this work was to create a database, namely LTDB, with a significant number of manually tracked leukocytes. Broad experimental conditions, sites of imaging, types of immune cells and challenging case studies were included to foster the development of robust computer vision techniques for imaging-based immunological research. Lastly, LTDB represents a step towards the unravelling of biological mechanisms by video data mining in systems biology
Fosforilação da HsPI3-Kinase-C2α = Phosphorylation of HsPI3-Kinase-C2α
No full textMestrado em Métodos Biomoleculares AvançadosVárias isoformas da enzima fosfoinositide-3-cinase (PI3-Cinase), uma vasta
família de cinases lipidicas têm nos últimos anos vindo a ser clonada e
caracterizada. P13-Cinases constituem uma família de cinases conservadas
durante a evolução que catalisam a adição de uma molécula de fosfato ao
fosfatidilinositol e seus derivados, esta adição tem lugar no anel inositol na
posição D3. P13-Cinases estão agrupadas em três classes de acordo com as
moléculas que preferencialmente utilizam como substrato in vitro e de acordo
com as suas características estruturais.
Fosfoinositide-3-Cinase-C2α (PI3-Cinase-C2α), pertence à classe I1 de P13-
Cinases, esta classe é caracterizada pela utilização de fosfatidilinositol e
fosfatidilinositol-4-P como substrato in vitro. Todos os membros da classes I1
possuem no seu C-terminal um domínio C2, característico da classe.
Este trabalho permitiu a identificação do local de fosforilação da HsPI3-Cinase-
C2α bem como a identificação de duas cinases envolvidas na sua fosforilação.
A fosforilação de HsP13-Kinase-C2α ocorre na Ser259 e este resíduo é um alvo
comum de fosforilação mitótica e de fosforilação induzida por radiação UV.
Durante o ciclo celular HsP13-Cinase-C2α é predominantemente fosforilada na M fase e a cinase envolvida 6 a Cdk1,após radiação UV a fosforilação é
mediada pela JNK.In recent years, a large family of Phosphoinositide-3-Kinases (PI3-Kinase)
isozymes has been characterized and cloned. PI3-Kinases constitute a family
of evolutionary conserved lipid kinases that catalyse the addition of a
phosphate molecule to the D3 position of the inositol ring of
phosphatidylinositol and its derivatives. P13-Kinases are grouped into three
classes according to the molecules that they preferentially utilize as substrates
and their structural characteristics.
Phosphoinositide-3-Kinase-C2α (P13-Kinase-C2α) belongs to class II P13-
Kinases, which are defined by their in vitro use of phosphatidylinositol and
phosphatidylinositol-4-phosphate as substrates. All type II P13-Kinases contain
a C2 domain at their C-terminus.
This work resulted in the identification of a phosphorylation site on HsP13-
Kinase-C2α as well the identification of two kinases involved in mitotic and UVinduced
phosphorylation of HsP13-Kinase-C2α. The phosphorylation of HsP13-
Kinase-C2α occurs in Ser259 and this serine is a common target in mitotic and
UV-induced phosphorylation. We found that during the cell cycle HsP13-
Kinase-C2α is predominantly phosphorylated in mitotic phase and the kinase
involved is Cdkl and after UV irradiation the phosphorylation of HsPI3-Kinase-
C2α is mediated by JNK
ACKR3 promotes CXCL12/CXCR4-mediated cell-to-cell-induced lymphoma migration through LTB4 production
No full textChemotaxis is an essential physiological process, often harnessed by tumors for metastasis. CXCR4, its ligand CXCL12 and the atypical receptor ACKR3 are overexpressed in many human cancers. Interfering with this axis by ACKR3 deletion impairs lymphoma cell migration towards CXCL12. Here, we propose a model of how ACKR3 controls the migration of the diffused large B-cell lymphoma VAL cells in vitro and in vivo in response to CXCL12. VAL cells expressing full-length ACKR3, but not a truncated version missing the C-terminus, can support the migration of VAL cells lacking ACKR3 (VAL-ko) when allowed to migrate together. This migration of VAL-ko cells is pertussis toxin-sensitive suggesting the involvement of a G(i)-protein coupled receptor. RNAseq analysis indicate the expression of chemotaxis-mediating LTB4 receptors in VAL cells. We found that LTB4 acts synergistically with CXCL12 in stimulating the migration of VAL cells. Pharmacologic or genetic inhibition of BLT(1)R markedly reduces chemotaxis towards CXCL12 suggesting that LTB4 enhances in a contact-independent manner the migration of lymphoma cells. The results unveil a novel mechanism of cell-to-cell-induced migration of lymphoma
An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15
No full textChemokines and their receptors are essential regulators of in vivo leukocyte migration and, some years ago, a systematic nomenclature system was developed for the chemokine receptor family. Chemokine receptor biology and biochemistry was recently extensively reviewed. In this review, we also highlighted a new component to the nomenclature system that incorporates receptors previously known as ‘scavenging’, or ‘decoy’, chemokine receptors on the basis of their lack of classical signalling responses to ligand binding and their general ability to scavenge, or sequester, their cognate chemokine ligands. These molecules are now collectively referred to as ‘atypical chemokine receptors’, or ACKRs, and play fundamental roles in regulating in vivo responses to chemokines. This commentary highlights this new addition to the chemokine receptor nomenclature system and provides brief information on the four receptors currently covered by this nomenclature
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