1,720,962 research outputs found
Targeting eukaryotic Rab proteins: a smart strategy for chlamydial survival and replication
Full text linkChlamydia, an obligate intracellular bacterium which passes its entire lifecycle within a membrane-bound vacuole called the inclusion, has evolved a variety of unique strategies to establish an advantageous intracellular niche for survival. This review highlights the mechanisms by which Chlamydia subverts vesicular transport in host cells, particularly by hijacking the master controllers of eukaryotic trafficking, the Rab proteins. A subset of Rabs and Rab interacting proteins that control the recycling pathway or the biosynthetic route are selectively recruited to the chlamydial inclusion membrane. By interfering with Rab-controlled transport steps, this intracellular pathogen not only prevents its own degradation in the phagocytic pathway, but also creates a favourable intracellular environment for growth and replication. Chlamydia, a highly adapted and successful intracellular pathogen, has several redundant strategies to re-direct vesicles emerging from biosynthetic compartments that carry host molecules essential for bacterial development. Although current knowledge is limited, the latest findings have shed light on the role of Rab proteins in the course of chlamydial infections and could open novel opportunities for anti-chlamydial therapy.Fil: Damiani, Maria Elena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Gambarte Tudela, Julian Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Cienicas Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; Argentin
Rab11-Family of Interacting Protein 2 associates with chlamydial inclusions through its Rab-binding domain and promotes bacterial multiplication
Full text linkChlamydia trachomatis, an obligate intracellular pathogen, survives within host cells in a special compartment named ‘inclusion’ and takes advantage of host vesicular transport pathways for its growth and replication. Rab GTPases are key regulatory proteins of intracellular trafficking. Several Rabs, among them Rab11 and Rab14, are implicated in chlamydial development. FIP2, a member of the Rab11-Family of Interacting Proteins, presents at the C-terminus a Rab-binding domain that interacts with both Rab11 and Rab14. In this study, we determined and characterized the recruitment of endogenous and GFP-tagged FIP2 to the chlamydial inclusions. The recruitment of FIP2 is specific since other members of the Rab11- Family of Interacting Proteins do not associate with the chlamydial inclusions. The Rab-binding domain of FIP2 is essential for its association. Our results indicate that FIP2 binds to Rab11 at the chlamydial inclusion membrane through its Rabbinding domain. The presence of FIP2 at the chlamydial inclusion favours the recruitment of Rab14. Furthermore, our results show that FIP2 promotes inclusion development and bacterial replication. In agreement, the silencing of FIP2 decreases the bacterial progeny. C. trachomatis likely recruits FIP2 to hijack host intracellular traf- ficking to redirect vesicles full of nutrients towards the inclusion.Fil: Leiva, Natalia Lorena. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histologia y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histologia y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; ArgentinaFil: Damiani, Maria Teresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Mendoza. Instituto Histologia y Embriología de Mendoza "Dr. M. Burgos"; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas; Argentin
MYO1C stabilizes actin and facilitates the arrival of transport carriers at the Golgi complex
Full text linkIn this study, we aimed to identify the myosin motor proteins that control trafficking at the Golgi complex. In addition to the known Golgi-associated myosins MYO6, MYO18A and MYH9 (myosin IIA), we identified MYO1C as a novel player at the Golgi in a human cell line. We demonstrate that depletion of MYO1C induces Golgi complex fragmentation and decompaction. MYO1C accumulates at dynamic structures around the Golgi complex that colocalize with Golgi-associated actin dots. MYO1C depletion leads to loss of cellular F-actin, and Golgi complex decompaction is also observed after inhibition or loss of the actin-related protein 2/3 complex, Arp2/3 (also known as ARPC). We show that the functional consequence of MYO1C depletion is a delay in the arrival of incoming transport carriers, both from the anterograde and retrograde routes. We propose that MYO1C stabilizes actin at the Golgi complex, facilitating the arrival of incoming transport carriers at the Golgi.This article has an associated First Person interview with the first author of the paper.Fil: Capmany, Anahi. Institute Curie; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Universidad Nacional de Cuyo. Facultad de Ciencias Medicas. Instituto de Inmunologia; ArgentinaFil: Yoshimura, Azumi. Institute Curie; FranciaFil: Kerdous, Rachid. Institute Curie; FranciaFil: Caorsi, Valentina. Abbelight; FranciaFil: Lescure, Aurianne. Institute Curie; FranciaFil: Nery, Elaine Del. Institute Curie; FranciaFil: Coudrier, Evelyne. Institute Curie; FranciaFil: Goud, Bruno. Institute Curie; FranciaFil: Schauer, Kristine. Institute Curie; Franci
Frustrated endocytosis controls contractility-independent mechanotransduction at clathrin-coated structures
Full text linkIt is generally assumed that cells interrogate the mechanical properties of their environment by pushing and pulling on the extracellular matrix (ECM). For instance, acto-myosin-dependent contraction forces exerted at focal adhesions (FAs) allow the cell to actively probe substrate elasticity. Here, we report that a subset of long-lived and flat clathrin-coated structures (CCSs), also termed plaques, are contractility-independent mechanosensitive signaling platforms. We observed that plaques assemble in response to increasing substrate rigidity and that this is independent of FAs, actin and myosin-II activity. We show that plaque assembly depends on αvβ5 integrin, and is a consequence of frustrated endocytosis whereby αvβ5 tightly engaged with the stiff substrate locally stalls CCS dynamics. We also report that plaques serve as platforms for receptor-dependent signaling and are required for increased Erk activation and cell proliferation on stiff environments. We conclude that CCSs are mechanotransduction structures that sense substrate rigidity independently of cell contractility.Fil: Baschieri, Francesco. Université Paris Sud; FranciaFil: Dayot, Stéphane. Université Paris Sud; Francia. Research University; FranciaFil: Elkhatib, Nadia. Université Paris Sud; FranciaFil: Ly, Nathalie. Université Paris Sud; FranciaFil: Capmany, Anahi. Centre National de la Recherche Scientifique; Francia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza; Argentina. Research University; FranciaFil: Schauer, Kristine. Research University; Francia. Centre National de la Recherche Scientifique; FranciaFil: Betz, Timo. University of Münster; AlemaniaFil: Vignjevic, Danijela Matic. Centre National de la Recherche Scientifique; Francia. Research University; FranciaFil: Poincloux, Renaud. Université de Toulouse; FranciaFil: Montagnac, Guillaume. Université Paris Sud; Franci
Akt/AS160 Signaling pathway inhibition impairs infection by decreasing rab14-controlled sphingolipids delivery to chlamydial inclusions
Full text linkChlamydia trachomatis, an obligate intracellular bacterium, intercepts different trafficking pathways of the host cell to acquire essential lipids for its survival and replication, particularly from the Golgi apparatus via a Rab14-mediated transport. Molecular mechanisms underlying how these bacteria manipulate intracellular transport are a matter of intense study. Here, we show that C. trachomatis utilizes Akt/AS160 signaling pathway to promote sphingolipids delivery to the chlamydial inclusion through Rab14-controlled vesicular transport. C. trachomatis provokes Akt phosphorylation along its entire developmental life cycle and recruits phosphorylated Akt (pAkt) to the inclusion membrane. As a consequence, Akt Substrate of 160 kDa (AS160), also known as TBC1D4, a GTPase Activating Protein (GAP) for Rab14, is phosphorylated and therefore inactivated. Phosphorylated AS160 (pAS160) loses its ability to promote GTP hydrolysis, favoring Rab14 binding to GTP. Akt inhibition by an allosteric isoform-specific Akt inhibitor (iAkt) prevents AS160 phosphorylation and reduces Rab14 recruitment to chlamydial inclusions. iAkt further impairs sphingolipids acquisition by C. trachomatis-inclusion and provokes lipid retention at the Golgi apparatus. Consequently, treatment with iAkt decreases chlamydial inclusion size, bacterial multiplication, and infectivity in a dose-dependent manner. Similar results were found in AS160-depleted cells. By electron microscopy, we observed that iAkt generates abnormal bacterial forms as those reported after sphingolipids deprivation or Rab14 silencing. Taken together, our findings indicate that targeting the Akt/AS160/Rab14 axis could constitute a novel strategy to limit chlamydial infections, mainly for those caused by antibiotic-resistant bacteria.Fil: Capmany, Anahi. Universidad de Mendoza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Abregú, Ángel Julián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Alonso Bivou, Mariano Ángel. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Damiani, María T.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Chlamydia trachomatis Infection Impairs MHC-I Intracellular Trafficking and Antigen Cross-Presentation by Dendritic Cells
Full text linkDuring cross-presentation, exogenous antigens (i.e. intracellular pathogens or tumor cells) are internalized and processed within the endocytic system and also by the proteasome in the cytosol. Then, antigenic peptides are associated with Major Histocompatibility Complex (MHC) class I molecules and these complexes transit to the plasma membrane in order to trigger cytotoxic immune responses through the activation of CD8+ T lymphocytes. Dendritic cells (DCs) are particularly adapted to achieve efficient antigen cross-presentation and their endocytic network displays important roles during this process, including a sophisticated MHC-I transport dependent on recycling compartments. In this study, we show that C. trachomatis, an obligate intracellular pathogen that exhibits multiple strategies to evade the immune system, is able to induce productive infections in the murine DC line JAWS-II. Our results show that when C. trachomatis infects these cells, the bacteria-containing vacuole strongly recruits host cell recycling vesicles, but no other endosomal compartments. Furthermore, we found that chlamydial infection causes significant alterations of MHC-I trafficking in JAWS-II DCs: reduced levels of MHC-I expression at the cell surface, disruption of the perinuclear MHC-I intracellular pool, and impairment of MHC-I endocytic recycling to the plasma membrane. We observed that all these modifications lead to a hampered cross-presentation ability of soluble and particulate antigens by JAWS-II DCs and primary bone marrow-derived DCs. In summary, our findings provide substantial evidence that C. trachomatis hijacks the DC endocytic recycling system, causing detrimental changes on MHC-I intracellular transport, which are relevant for competent antigen cross-presentation.Fil: del Balzo, Diego Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaFil: Damiani, Armando Mario. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Cebrián, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; Argentin
Chlamydia trachomatis causes the intracellular redistribution of MHC-I and impairs antigen presentation in dendritic cells
Full text linkChlamydia trachomatis (CT) is the most frequent bacterial cause of sexually transmitted infections worldwide. This highly adapted intracellular bacterium has evolved multiple strategies to hide inside cells. However, little is known about the molecular mechanisms underlying CT evasion of the immune response. Dendritic cells (DCs) are the most efficient antigen-presenting cells of the immune system and, an essential link between innate and adaptive immunity. Therefore, DCs could play a key role in CT´s clearance. In this study, we analyzed in CT-infected DCs the process of cross-presentation, in which exogenous antigens are associated with MHC-I molecules to activate CD8+ T lymphocytes. By confocal microscopy and flow cytometry-based approaches, we observed, after chlamydial infection, a decrease in MHC-I molecules exposed at the plasma membrane while they are redistributed intracellularly. However, the total amount of MHC-I molecules did not change after infection, as assessed by western blot analysis. Finally, we found that CT-infected DCs were less efficient than non-infected ones to cross-present the model antigen Ovalbumin, as measured colorimetrically by the activation of the antigen-specific CD8+ T cell hybrid called B3Z. Altogether, these findings indicate that CT infection impairs antigen-cross presentation in DCs through the disturbance of MHC-I transport.Fil: del Balzo, Diego Damián. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Capmany, Anahi. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Cebrián, José Ignacio. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Instituto de Histología y Embriología de Mendoza Dr. Mario H. Burgos; ArgentinaFil: Damiani, María ElenaTeresa. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mendoza. Instituto de Medicina y Biología Experimental de Cuyo; ArgentinaLV Reunión Anual de la Sociedad Argentina de Investigaciones en Bioquímica y Biología Molecular; XIV Conferencia de la Asociación Panamericana de Bioquímica y Biología MolecularSaltaArgentinaSociedad Argentina de Investigaciones en Bioquímica y Biología MolecularAsociación Panamericana de Bioquímica y Biología Molecula
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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