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1.
Athman R Louvard D Robine S 《American journal of physiology. Gastrointestinal and liver physiology》2002,283(3):G496-G502
Villin plays a key role in the maintenance of the brush border organization by bundling F-actin into a network of parallel filaments. Our previous in vivo data on villin knockout mice showed that, although this protein is not necessary for the bundling of F-actin, it is important for the reorganization of the actin cytoskeleton elicited by stress conditions. We further investigated villin property to initiate actin remodeling in cellular processes such as hepatocyte growth factor-induced motility, morphogenesis, and bacterial infection. Our data suggest that villin is involved in actin remodeling necessary for many cellular processes requiring the actin cytoskeleton plasticity. 相似文献
2.
Villin enhances hepatocyte growth factor-induced actin cytoskeleton remodeling in epithelial cells
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Villin is an actin-binding protein localized to intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a calcium-dependent manner. Although villin is not necessary for the bundling of F-actin in vivo, it is important for the reorganization of the actin cytoskeleton elicited by stress during both physiological and pathological conditions (Ferrary et al., 1999). These data suggest that villin may be involved in actin cytoskeleton remodeling necessary for many processes requiring cellular plasticity. Here, we study the role of villin in hepatocyte growth factor (HGF)-induced epithelial cell motility and morphogenesis. For this purpose, we used primary cultures of enterocytes derived from wild-type and villin knock-out mice and Madin-Darby canine kidney cells, expressing villin in an inducible manner. In vitro, we show that epithelial cell lysates from villin-expressing cells induced dramatic, calcium-dependent severing of actin filaments. In cell culture, we found that villin-expressing cells exhibit enhanced cell motility and morphogenesis upon HGF stimulation. In addition, we show that the ability of villin to potentiate HGF-induced actin reorganization occurs through the HGF-activated phospholipase Cgamma signaling pathway. Collectively, these data demonstrate that villin acts as a regulator of HGF-induced actin dynamics. 相似文献
3.
Athman R Fernandez MI Gounon P Sansonetti P Louvard D Philpott D Robine S 《Cellular microbiology》2005,7(8):1109-1116
Villin is an actin-binding protein present in intestinal and kidney brush borders. Villin has been shown to present in vitro Ca(2+)-dependent bundling and severing F-actin properties. The study of villin knock-out mice allowed us to show that while bundling of F-actin microfilaments is unaffected, this protein is important for the reorganization of the actin cytoskeleton elicited by various signals during both physiological and pathological conditions. Here, we studied the role of villin during infection by Shigella flexneri, the causative agent of bacillary dysentery. This bacterium induces the reorganization of the host actin cytoskeleton to penetrate into epithelial cells and spread from cell to cell. In vivo, we show that unlike newborn vil+/+ mice, which are sensitive to Shigella invasion, resulting in a destructive inflammatory response of the intestinal mucosa following intragastric inoculation, newborn vil-/- mice appear fully resistant to infection. Using primary cultures of intestinal epithelial cells derived from vil+/+ or vil -/- mice, we demonstrate that villin plays an essential role in S. flexneri entry and cell-to-cell dissemination. Villin expression is thus critical for Shigella infection through its ability to remodel the actin cytoskeleton. 相似文献
4.
E Ferrary M Cohen-Tannoudji G Pehau-Arnaudet A Lapillonne R Athman T Ruiz L Boulouha F El Marjou A Doye J J Fontaine C Antony C Babinet D Louvard F Jaisser S Robine 《The Journal of cell biology》1999,146(4):819-830
Villin is an actin-binding protein localized in intestinal and kidney brush borders. In vitro, villin has been demonstrated to bundle and sever F-actin in a Ca(2+)-dependent manner. We generated knockout mice to study the role of villin in vivo. In villin-null mice, no noticeable changes were observed in the ultrastructure of the microvilli or in the localization and expression of the actin-binding and membrane proteins of the intestine. Interestingly, the response to elevated intracellular Ca(2+) differed significantly between mutant and normal mice. In wild-type animals, isolated brush borders were disrupted by the addition of Ca(2+), whereas Ca(2+) had no effect in villin-null isolates. Moreover, increase in intracellular Ca(2+) by serosal carbachol or mucosal Ca(2+) ionophore A23187 application abolished the F-actin labeling only in the brush border of wild-type animals. This F-actin disruption was also observed in physiological fasting/refeeding experiments. Oral administration of dextran sulfate sodium, an agent that causes colonic epithelial injury, induced large mucosal lesions resulting in a higher death probability in mice lacking villin, 36 +/- 9.6%, compared with wild-type mice, 70 +/- 8.8%, at day 13. These results suggest that in vivo, villin is not necessary for the bundling of F-actin microfilaments, whereas it is necessary for the reorganization elicited by various signals. We postulate that this property might be involved in cellular plasticity related to cell injury. 相似文献
5.
Shahasi Y. Athman Thomas Dubois Daniel Coyne Clifford S. Gold Nico Labuschagne Altus Viljoen 《Journal of nematology》2006,38(4):455-460
The burrowing nematode Radopholus similis is one of the major constraints to banana (Musa spp.) production worldwide. Resource-poor farmers can potentially manage R. similis by using naturally occurring banana endophytes, such as nonpathogenic Fusarium oxysporum, that are inoculated into tissue culture banana plantlets. At present, it is unclear at what stage in the R. similis infection process the endophytes are most effective. In this study, the effect of three endophytic F. oxysporum isolates (V5w2, Eny1.31i and Eny7.11o) on R. similis host preference of either endophyte-treated or untreated banana plants was investigated. No differences were observed between the proportion of nematodes attracted to either root segments excised from endophyte-treated or untreated plants, or in experiments using endophyte-treated and untreated tissue culture banana plantlets. These results imply that the early processes of banana plant host recognition by R. similis are not affected by endophyte infection. 相似文献
6.
Matthew Gilliham Asmini Athman Stephen D. Tyerman Simon J. Conn 《Plant signaling & behavior》2011,6(11):1656-1661
Vacuoles of different leaf cell-types vary in their capacity to store specific mineral elements. In Arabidopsis thaliana potassium (K) accumulates preferentially in epidermal and bundle sheath cells whereas calcium (Ca) and magnesium (Mg) are stored at high concentrations only in mesophyll cells. Accumulation of these elements in a particular vacuole can be reciprocal, i.e. as [K]vac increases [Ca]vac decreases. Mesophyll-specific Ca-storage involves CAX1 (a Ca2+/H+ antiporter) and Mg-storage involves MRS2-1/MGT2 and MRS2-5/MGT3 (both Mg2+-transporters), all of which are preferentially expressed in the mesophyll and encode tonoplast-localised proteins. However, what controls leaf-cell [K]vac is less well understood. TPC1 encodes the two-pore Ca2+ channel protein responsible for the tonoplast-localised SV cation conductance, and is highly expressed in cell-types that not preferentially accumulate Ca. Here, we evaluate evidence that TPC1 has a role in maintaining differential K and Ca storage across the leaf, and propose a function for TPC1 in releasing Ca2+ from epidermal and bundle sheath cell vacuoles to maintain low [Ca]vac. Mesophyll-specific Ca storage is essential to maintain apoplastic free Ca concentration at a level that does not perturb a range of physiological parameters including leaf gas exchange, cell wall extensibility and growth. When plants are grown under serpentine conditions (high Mg/Ca ratio), MGT2/MRS2-1 and MGT3/MRS2-5 are required to sequester additional Mg2+ in vacuoles to replace Ca2+ as an osmoticum to maintain growth. An updated model of Ca2+ and Mg2+ transport in leaves is presented as a reference for future interrogation of nutritional flows and elemental storage in plant leaves. 相似文献
7.
Supriya Shukla Edward T. Richardson Jaffre J. Athman Libin Shi Pamela A. Wearsch David McDonald Niaz Banaei W. Henry Boom Mary Jackson Clifford V. Harding 《PLoS pathogens》2014,10(10)
Mycobacterium tuberculosis (Mtb) virulence is decreased by genetic deletion of the lipoprotein LprG, but the function of LprG remains unclear. We report that LprG expressed in Mtb binds to lipoglycans, such as lipoarabinomannan (LAM), that mediate Mtb immune evasion. Lipoglycan binding to LprG was dependent on both insertion of lipoglycan acyl chains into a hydrophobic pocket on LprG and a novel contribution of lipoglycan polysaccharide components outside of this pocket. An lprG null mutant (Mtb ΔlprG) had lower levels of surface-exposed LAM, revealing a novel role for LprG in determining the distribution of components in the Mtb cell envelope. Furthermore, this mutant failed to inhibit phagosome-lysosome fusion, an immune evasion strategy mediated by LAM. We propose that LprG binding to LAM facilitates its transfer from the plasma membrane into the cell envelope, increasing surface-exposed LAM, enhancing cell envelope integrity, allowing inhibition of phagosome-lysosome fusion and enhancing Mtb survival in macrophages. 相似文献
8.
Dubourdeau M Athman R Balloy V Huerre M Chignard M Philpott DJ Latgé JP Ibrahim-Granet O 《Journal of immunology (Baltimore, Md. : 1950)》2006,177(6):3994-4001
Aspergillus fumigatus causes invasive aspergillosis in immunosuppressed patients. In the immunocompetent host, inhaled conidia are cleared by alveolar macrophages. The signaling pathways of the alveolar macrophage involved in the clearance of A. fumigatus are poorly understood. Therefore, we investigated the role of TLRs in the immune response against A. fumigatus and their contribution to the signaling events triggered in murine alveolar macrophages upon infection with A. fumigatus conidia. Specifically, we examined the MAPKs and NF-kappaB activation and cytokine signaling. Our investigations revealed that immunocompetent TLR2, TLR4, and MyD88 knockout mice were not more susceptible to invasive aspergillosis as compared with wild-type mice and that the in vitro phosphorylation of the MAPKs ERK and p38 was not affected in TLR2, TLR4, or MyD88 knockout mice following stimulation with conidia. In vivo experiments suggest that ERK was an essential MAPK in the defense against A. fumigatus, whereas the activation of NF-kappaB appeared to play only a secondary role. In conclusion, our findings demonstrate that TLR2/4 recognition and MyD88 signaling are dispensable for the clearance of A. fumigatus under immunocompetent situations. Furthermore, our data stress the important role of ERK activation in innate immunity to A. fumigatus. 相似文献
9.
The sodium transporter encoded by the HKT1;2 gene modulates sodium/potassium homeostasis in tomato shoots under salinity
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Noelia Jaime‐Pérez Benito Pineda Begoña García‐Sogo Alejandro Atares Asmini Athman Caitlin S. Byrt Raquel Olías Maria José Asins Matthew Gilliham Vicente Moreno Andrés Belver 《Plant, cell & environment》2017,40(5):658-671
Excessive soil salinity diminishes crop yield and quality. In a previous study in tomato, we identified two closely linked genes encoding HKT1‐like transporters, HKT1;1 and HKT1;2, as candidate genes for a major quantitative trait locus (kc7.1) related to shoot Na+/K+ homeostasis – a major salt tolerance trait – using two populations of recombinant inbred lines (RILs). Here, we determine the effectiveness of these genes in conferring improved salt tolerance by using two near‐isogenic lines (NILs) that were homozygous for either the Solanum lycopersicum allele (NIL17) or for the Solanum cheesmaniae allele (NIL14) at both HKT1 loci; transgenic lines derived from these NILs in which each HKT1;1 and HKT1;2 had been silenced by stable transformation were also used. Silencing of ScHKT1;2 and SlHKT1;2 altered the leaf Na+/K+ ratio and caused hypersensitivity to salinity in plants cultivated under transpiring conditions, whereas silencing SlHKT1;1/ScHKT1;1 had a lesser effect. These results indicate that HKT1;2 has the more significant role in Na+ homeostasis and salinity tolerance in tomato. 相似文献
10.
Munns R James RA Xu B Athman A Conn SJ Jordans C Byrt CS Hare RA Tyerman SD Tester M Plett D Gilliham M 《Nature biotechnology》2012,30(4):360-364
The ability of wheat to maintain a low sodium concentration ([Na(+)]) in leaves correlates with improved growth under saline conditions. This trait, termed Na(+) exclusion, contributes to the greater salt tolerance of bread wheat relative to durum wheat. To improve the salt tolerance of durum wheat, we explored natural diversity in shoot Na(+) exclusion within ancestral wheat germplasm. Previously, we showed that crossing of Nax2, a gene locus in the wheat relative Triticum monococcum into a commercial durum wheat (Triticum turgidum ssp. durum var. Tamaroi) reduced its leaf [Na(+)] (ref. 5). Here we show that a gene in the Nax2 locus, TmHKT1;5-A, encodes a Na(+)-selective transporter located on the plasma membrane of root cells surrounding xylem vessels, which is therefore ideally localized to withdraw Na(+) from the xylem and reduce transport of Na(+) to leaves. Field trials on saline soils demonstrate that the presence of TmHKT1;5-A significantly reduces leaf [Na(+)] and increases durum wheat grain yield by 25% compared to near-isogenic lines without the Nax2 locus. 相似文献