Función de las tetraspaninas y proteínas del citoesqueleto cortical de actina en la entradadel virus de la inmunodeficiencia humana (VIH-1)

Tesis doctoral inédita leida en la Universidad Autónoma de Madrid. Facultad de Medicina. Departamento de Bioquímica. Fecha de lectura: 23 de Noviembre de 200

MTOC translocation modulates IS formation and controls sustained T cell signaling

The translocation of the microtubule-organizing center (MTOC) toward the nascent immune synapse (IS) is an early step in lymphocyte activation initiated by T cell receptor (TCR) signaling. The molecular mechanisms that control the physical movement of the lymphocyte MTOC remain largely unknown. We have studied the role of the dynein–dynactin complex, a microtubule-based molecular motor, in the process of T cell activation during T cell antigen–presenting cell cognate immune interactions. Impairment of dynein–dynactin complex activity, either by overexpressing the p50-dynamitin component of dynactin to disrupt the complex or by knocking down dynein heavy chain expression to prevent its formation, inhibited MTOC translocation after TCR antigen priming. This resulted in a strong reduction in the phosphorylation of molecules such as ζ chain–associated protein kinase 70 (ZAP70), linker of activated T cells (LAT), and Vav1; prevented the supply of molecules to the IS from intracellular pools, resulting in a disorganized and dysfunctional IS architecture; and impaired interleukin-2 production. Together, these data reveal MTOC translocation as an important mechanism underlying IS formation and sustained T cell signaling

The PDZ-adaptor protein syntenin-1 regulates HIV-1 entry

Syntenin-1 is a cytosolic adaptor protein involved in several cellular processes requiring polarization. Human immunodeficiency virus type 1 (HIV-1) attachment to target CD4(+) T-cells induces polarization of the viral receptor and coreceptor, CD4/CXCR4, and cellular structures toward the virus contact area, and triggers local actin polymerization and phosphatidylinositol 4,5-bisphosphate (PIP(2)) production, which are needed for successful HIV infection. We show that syntenin-1 is recruited to the plasma membrane during HIV-1 attachment and associates with CD4, the main HIV-1 receptor. Syntenin-1 overexpression inhibits HIV-1 production and HIV-mediated cell fusion, while syntenin depletion specifically increases HIV-1 entry. Down-regulation of syntenin-1 expression reduces F-actin polymerization in response to HIV-1. Moreover, HIV-induced PIP(2) accumulation is increased in syntenin-1–depleted cells. Once the virus has entered the target cell, syntenin-1 polarization toward the viral nucleocapsid is lost, suggesting a spatiotemporal regulatory role of syntenin-1 in actin remodeling, PIP(2) production, and the dynamics of HIV-1 entry

Ecos de la academia: Revista de la Facultad de Educación, Ciencia y Tecnología - FECYT Nro 5

Ecos de la academia, Revista de la Facultad de Educación Ciencia y Tecnología es una publicación científica de la Universidad Técnica del Norte, con revisión por pares a doble ciego que publica artículos en idioma español, quichua, portugués e inglés. Se edita con una frecuencia semestral con dos números por año.En ella se divulgan trabajos originales e inéditos generados por los investigadores, docentes y estudiantes de la FECYT, y contribuciones de profesionales de instituciones docentes e investigativas dentro y fuera del país, con calidad, originalidad y relevancia en las áreas de ciencias sociales y tecnología aplicada.Realidad socioinclusiva del adulto mayor del grupo etario mayor a los 70 años en las parroquias urbanas de Ibarra. Orientación vocacional y personalidad en el Sistema Nacional de Nivelación y Admisión en la Universidad Técnica de Ambato. Las primeras tarjetas postales de Ibarra, Ecuador: 1906-1914. Aprendizaje móvil en el aula. Aproximación a la Concepción Etnomatemática. La ética en la investigación educativa: ¿condición indispensable?. Inteligencia sociocultural para la inclusión. Atención al alumnado inmigrante: la visión de una profesora francesa en Galicia. Análisis crítico de la dimensión ambiental del ecosistema montañoso Guamuhaya, Cuba (1995-2014). La adaptación curricular inclusiva en la educación regular. El arte en la provincia de Imbabura de mediados del siglo XIX en torno a las escuelas de arte. Formación integral: un estudio de algunos logros y carencias. Experiencias en la publicidad online en la ciudad de Ibarra, Ecuador. Estudio exploratorio de la incidencia de los hogares disfuncionales en la iniciación sexual temprana de los adolescentes. Etnografía Virtual como aplicación metodológica: Caso Chevron en Ecuador. Alfabetización y calidad de vida: percepción de los alfabetizados. Elaboración de un manual mediante el método Delphi para la enseñanza de patronaje. Pertinencia de la Carrera de Turismo de la UTN, en el contexto de la Región 1 del Ecuador, 2016-2020. Preferencias por doble titulación de bachilleres de la Zona 1 de Ecuador y Nariño de Colombia. “Mucha Publicidad”, II Simposio de Diseño, Publicidad y Sociedad, de la UTN. Normas de presentación de artículos en la revista Ecos de la Academia

Role of Fyn in the rearrangement of tubulin cytoskeleton induced through TCR.

The translocation of the microtubule-organizing center (MTOC), its associated signaling complex, and the secretory apparatus is the most characteristic early event that involves the tubulin cytoskeleton of T or NK cells after their interaction with APC or target cells. Our results show that Fyn kinase activity is essential for MTOC reorientation in an Ag-dependent system. Moreover, T cells from Fyn-deficient mice are unable to rearrange their tubulin cytoskeleton in response to anti-CD3-coated beads. Analysis of conjugates of T cells from transgenic OT-I mice with dendritic cells revealed that an antagonist peptide induces translocation of the MTOC, and that this process is impaired in T cells from Fyn(-/-) OT-I mice. In addition, Fyn deficiency significantly affects the MTOC relocation mediated by agonist peptide stimulation. These results reveal Fyn to be a key regulator of tubulin cytoskeleton reorganization in T cells

CD69 downregulates autoimmune reactivity through active transforming growth factor-β production in collagen-induced arthritis

CD69 is induced after activation of leukocytes at inflammatory sites, but its physiological role during inflammation remains unknown. We explored the role of CD69 in autoimmune reactivity by analyzing a model of collagen-induced arthritis (CIA) in WT and CD69-deficient mice. CD69–/– mice showed higher incidence and severity of CIA, with exacerbated T and B cell immune responses to type II collagen. Levels of TGF-β1 and TGF-β2, which act as protective agents in CIA, were reduced in CD69–/– mice inflammatory foci, correlating with the increase in the proinflammatory cytokines IL-1β and RANTES. Local injection of blocking anti–TGF-β antibodies increased CIA severity and proinflammatory cytokine mRNA levels in CD69+/+ but not in CD69–/– mice. Moreover, in vitro engagement of CD69 induced total and active TGF-β1 production in Concanavalin A–activated splenocyte subsets, mouse and human synovial leukocytes, and Jurkat stable transfectants of human CD69 but not in the parental CD69 negative cell line. Our results show that CD69 is a negative modulator of autoimmune reactivity and inflammation through the synthesis of TGF-β, a cytokine that in turn downregulates the production of various proinflammatory mediators.Peer reviewe

(A) CD69 induction was detected by flow cytometry in J77 Jurkat clones overexpressing GFP or p50-dynamitin-GFP (c) and conjugated with unprimed or SEE-pulsed Raji APC for 16 h (percentage of cells is shown)

Three experiments were performed in triplicate. (B and C) IL-2 was detected by ELISA in culture supernatants (B) or cell lysates (C) from the cultures in A. Three experiments were performed in triplicate. (D) IL-2 detected by ELISA in cell supernatants from DHC-silenced J77 cells (siDHC, closed bars) and controls (siNeg, open bars) conjugated with SEE-pulsed Raji APC with the indicated doses (μg/ml). Three experiments were performed in triplicate. Data are means ± SD. *, P < 0.05; **, P < 0.001 (Student's test).<p><b>Copyright information:</b></p><p>Taken from "MTOC translocation modulates IS formation and controls sustained T cell signaling"</p><p></p><p>The Journal of Cell Biology 2008;182(5):951-962.</p><p>Published online 8 Sep 2008</p><p>PMCID:PMC2528574.</p><p></p

F-actin-binding protein drebrin regulates CXCR4 recruitment to the immune synapse

Acknowledgements This work was partly supported by EU-México FONCICYT –C002-2008-1 ALA/127249, SAF-2008-02635, INSINET 01592006 CAM, Red RECAVA RD06/0014-0030 and FIPSE 36658/07 grants. E.V.C. holds a Ramón y Cajal contract from the Spanish Ministry of Science and Innovation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank H. de la Fuente for statistical assistance. Editorial assistance was provided by S. Bartlett. G.M. is supported by the European Union-funded International Graduate Program in Molecular Medicine.The adaptive immune response depends on the interaction of T cells and antigen-presenting cells at the immune synapse. Formation of the immune synapse and the subsequent T-cell activation are highly dependent on the actin cytoskeleton. In this work, we describe that T cells express drebrin, a neuronal actin-binding protein. Drebrin colocalizes with the chemokine receptor CXCR4 and F-actin at the peripheral supramolecular activation cluster in the immune synapse. Drebrin interacts with the cytoplasmic tail of CXCR4 and both proteins redistribute to the immune synapse with similar kinetics. Drebrin knockdown in T cells impairs the redistribution of CXCR4 and inhibits actin polymerization at the immune synapse as well as IL-2 production. Our data indicate that drebrin exerts an unexpected and relevant functional role in T cells during the generation of the immune response.Depto. de Biología CelularFac. de Ciencias BiológicasTRUEpu