[Variations on the theme of podosomes, context matters].

Podosomes are actin-based microdomains connecting the cell with its extracellular matrix. Contractile actin-myosin cables assemble them into a network that constitutes a versatile cellular superstructure. Discovered and extensively described in in vitro conditions, podosomes now appear as major actors of specific physiological processes.

Variations on the theme of podosomes: A matter of context.

Extensive in vitro studies have described podosomes as actin-based structures at the plasma membrane, connecting the cell with its extracellular matrix and endowed with multiple capabilities. Contractile actin-myosin cables assemble them into a network that constitutes a multifaceted cellular superstructure taking different forms - with common characteristics - but manifesting different properties depending on the context of study. Their morphology and their role in cell functioning and behavior are therefore now apprehended in in vivo or in vitro situations relevant to physiological processes.

VEGF-A/Notch-Induced Podosomes Proteolyse Basement Membrane Collagen-IV during Retinal Sprouting Angiogenesis.

During angiogenic sprouting, endothelial tip cells emerge from existing vessels in a process that requires vascular basement membrane degradation. Here, we show that F-actin/cortactin/P-Src-based matrix-degrading microdomains called podosomes contribute to this step. In vitro, VEGF-A/Notch signaling regulates the formation of functional podosomes in endothelial cells.

Podosomes: Multipurpose organelles?

Thirty years of research have accumulated ample evidence that podosome clusters qualify as genuine cellular organelles that are being found in more and more cell types. A podosome is a dynamic actin-based and membrane-bound microdomain and the organelle consists in an interconnected network of such basic units, forming a cytoskeletal superstructure linked to the plasma membrane. At this strategic location, podosomes are privileged sites of interactions with the pericellular environment that regulates their formation, density, lifetime, distribution, architecture and functioning.

Importance of RhoGTPases in formation, characteristics, and functions of invadosomes.

Podosomes and invadopodia (collectively known as invadosomes) are specialized plasma-membrane actin-based microdomains that combine adhesive properties with matrix degrading and/or mechanosensor activities. These organelles have been extensively studied in vitro and current concerted efforts aim at establishing their physiological relevance and subsequent association with human diseases. Proper functioning of the bone, immune, and vascular systems is likely to depend on these structures while their occurrence in cancer cells appears to be linked to tumor metastasis.

Education catching up with science: preparing students for three-dimensional literacy in cell biology.

The large number of experimentally determined molecular structures has led to the development of a new semiotic system in the life sciences, with increasing use of accurate molecular representations. To determine how this change impacts students' learning, we incorporated image tests into our introductory cell biology course. Groups of students used a single text dealing with signal transduction, which was supplemented with images made in one of three iconographic styles.

Analysis of students' aptitude to provide meaning to images that represent cellular components at the molecular level.

The number of experimentally derived structures of cellular components is rapidly expanding, and this phenomenon is accompanied by the development of a new semiotic system for teaching. The infographic approach is shifting from a schematic toward a more realistic representation of cellular components. By realistic we mean artist-prepared or computer graphic images that closely resemble experimentally derived structures and are characterized by a low level of styling and simplification.

TGFbeta1 regulates endothelial cell spreading and hypertrophy through a Rac-p38-mediated pathway.

Background Information: TGFbeta (transforming growth factor beta) is a multifunctional cytokine and a potent regulator of cell growth, migration and differentiation in many cell types. In the vascular system, TGFbeta plays crucial roles in vascular remodelling, but the signalling pathways involved remain poorly characterized.

Results: Using the model of porcine aortic endothelial cells, we demonstrated that TGFbeta stimulates cellular spreading when cells are on collagen I.

Meeting report: teaching signal transduction.

In July, 2005, the European Institute of Chemistry and Biology at the campus of the University of Bordeaux, France, hosted a focused week of seminars, workshops, and discussions around the theme of "teaching signal transduction." The purpose of the summer school was to offer both junior and senior university instructors a chance to reflect on the development and delivery of their teaching activities in this area. This was achieved by combining open seminars with restricted access workshops and discussion events.

Transforming growth factor beta induces rosettes of podosomes in primary aortic endothelial cells.

Cytoskeletal rearrangements are central to endothelial cell physiology and are controlled by soluble factors, matrix proteins, cell-cell interactions, and mechanical forces. We previously reported that aortic endothelial cells can rearrange their cytoskeletons into complex actin-based structures called podosomes when a constitutively active mutant of Cdc42 is expressed. We now report that transforming growth factor beta (TGF-beta) promotes podosome formation in primary aortic endothelial cells.

CD44 and TGFbeta1 synergise to induce expression of a functional NADPH oxidase in promyelocytic cells.

Bone marrow stromal cells produce large amounts of extracellular matrix and cytokines. Amongst them, hyaluronan, a glycosaminoglycan and ligand for the cell surface molecule CD44, and TGFbeta1, a cytokine particularly important in monocyte differentiation. We have studied in vitro the role of hyaluronan and TGFbeta1 in the differentiation process of U937 monocytic progenitor cells.

RhoGTPases and p53 are involved in the morphological appearance and interferon-alpha response of hairy cells.

Hairy cell leukemia is an uncommon B-cell lymphoproliferative disease of unknown etiology in which tumor cells display characteristic microfilamentous membrane projections. Another striking feature of the disease is its exquisite sensitivity to interferon (IFN)-alpha. So far, none of the known IFN-alpha regulatory properties have explained IFN-alpha responsiveness nor have they taken into account the morphological characteristics of hairy cells.

Inhibitory control of TGF-beta1 on the activation of Rap1, CD11b, and transendothelial migration of leukocytes.

Beta2-integrins are a family of dimeric adhesion molecules expressed on leukocytes. Their capacity to bind ligand is regulated by their state of activation. CD11b, an alphaMbeta2 integrin, is implicated in a number of physiological and pathological events such as inflammation, thrombosis, or atherosclerosis.

Rheumatoid arthritis: targeting the proliferative fibroblasts.

Our flexible joints are synovial joints composed of bone, hyaline cartilage, synovial membrane, ligaments and tendons. Rheumatoid arthritis is a disease that affects multiple synovial joints and involves inflammation of the synovial membrane, often resulting in loss of function due to erosion of bone and cartilage. Inflammation is accompanied by an influx of immune-competent cells and by aberrant proliferation of resident fibroblast-like synoviocytes.

Influence of epitopes CD44v3 and CD44v6 in the invasive behavior of fibroblast-like synoviocytes derived from rheumatoid arthritic joints.

Objective: To investigate the functional implications of CD44 splice variant expression in fibroblast-like synoviocytes (FLS) obtained from patients with rheumatoid arthritis (RA).

Methods: FLS were isolated from synovial tissue obtained from both diseased and nondiseased joints. The expression of splice variants containing exons v3 and v6 was analyzed using immunocytochemistry with exon-specific antibodies and reverse transcription-polymerase chain reaction followed by Southern blotting.