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排序方式: 共有109条查询结果,搜索用时 15 毫秒
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MR Dores MM Paing H Lin WA Montagne A Marchese J Trejo 《Molecular biology of the cell》2012,23(18):3612-3623
The sorting of signaling receptors within the endocytic system is important for appropriate cellular responses. After activation, receptors are trafficked to early endosomes and either recycled or sorted to lysosomes and degraded. Most receptors trafficked to lysosomes are modified with ubiquitin and recruited into an endosomal subdomain enriched in hepatocyte growth factor-regulated tyrosine kinase substrate (HRS), a ubiquitin-binding component of the endosomal-sorting complex required for transport (ESCRT) machinery, and then sorted into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs)/lysosomes. However, not all receptors use ubiquitin or the canonical ESCRT machinery to sort to MVBs/lysosomes. This is exemplified by protease-activated receptor-1 (PAR1), a G protein-coupled receptor for thrombin, which sorts to lysosomes independent of ubiquitination and HRS. We recently showed that the adaptor protein ALIX binds to PAR1, recruits ESCRT-III, and mediates receptor sorting to ILVs of MVBs. However, the mechanism that initiates PAR1 sorting at the early endosome is not known. We now report that the adaptor protein complex-3 (AP-3) regulates PAR1 ubiquitin-independent sorting to MVBs through an ALIX-dependent pathway. AP-3 binds to a PAR1 cytoplasmic tail-localized tyrosine-based motif and mediates PAR1 lysosomal degradation independent of ubiquitination. Moreover, AP-3 facilitates PAR1 interaction with ALIX, suggesting that AP-3 functions before PAR1 engagement of ALIX and MVB/lysosomal sorting. 相似文献
64.
Combination of microwell structures and direct oxygenation enables efficient and size‐regulated aggregate formation of an insulin‐secreting pancreatic β‐cell line 下载免费PDF全文
Marie Shinohara Hiroshi Kimura Kevin Montagne Kikuo Komori Teruo Fujii Yasuyuki Sakai 《Biotechnology progress》2014,30(1):178-187
Spherical three‐dimensional (3D) cellular aggregates are valuable for various applications such as regenerative medicine or cell‐based assays due to their stable and high functionality. However, previous methods to form aggregates have shown drawbacks, being labor‐intensive, showing low productivity per unit area or volume and difficulty to form homogeneous aggregates. We proposed a novel strategy based on oxygen‐permeable polydimethylsiloxane (PDMS) honeycomb microwell sheets, which can theoretically supply about 80 times as much oxygen as conventional polystyrene culture dishes, to produce recoverable aggregates in controllable sizes using mouse insulinoma cells (MIN6‐m9). In 48 hours of culture, the PDMS sheets produced aggregates whose diameters were strictly controlled (?32, 60, 90, 150 and 280 mm) even at an inoculum density eight times higher (8.0×105 cells/cm2) than that of normal confluent monolayers (1.0×105 cells/cm2). Measurement of the oxygen tension near the cell layer and glucose/lactate analysis clearly showed that cells exhibit aerobic respiration on the PDMS‐based culture system. Glucose‐responsive insulin secretion of the recovered aggregates showed that the aggregates around 90 mm in diameter secreted the largest amounts of insulin. This confirmed the advantages of 3D cellular organization and the existence of a suitable aggregate size, above which excess organization leads to a decreased metabolic response. These results demonstrated that this microwell‐based PDMS culture system provides a promising method to form size‐regulated and better functioning 3D cellular aggregates of various kinds of cells with a high yield per surface area. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:178–187, 2014 相似文献
65.
Maelle Devilliers Damien Garrido Mickael Poidevin Thomas Rubin Arnaud Le Rouzic Jacques Montagne 《Genetics》2021,217(1):1
Glycolysis and fatty acid (FA) synthesis directs the production of energy-carrying molecules and building blocks necessary to support cell growth, although the absolute requirement of these metabolic pathways must be deeply investigated. Here, we used Drosophila genetics and focus on the TOR (Target of Rapamycin) signaling network that controls cell growth and homeostasis. In mammals, mTOR (mechanistic-TOR) is present in two distinct complexes, mTORC1 and mTORC2; the former directly responds to amino acids and energy levels, whereas the latter sustains insulin-like-peptide (Ilp) response. The TORC1 and Ilp signaling branches can be independently modulated in most Drosophila tissues. We show that TORC1 and Ilp-dependent overgrowth can operate independently in fat cells and that ubiquitous over-activation of TORC1 or Ilp signaling affects basal metabolism, supporting the use of Drosophila as a powerful model to study the link between growth and metabolism. We show that cell-autonomous restriction of glycolysis or FA synthesis in fat cells retrains overgrowth dependent on Ilp signaling but not TORC1 signaling. Additionally, the mutation of FASN (Fatty acid synthase) results in a drop in TORC1 but not Ilp signaling, whereas, at the cell-autonomous level, this mutation affects none of these signals in fat cells. These findings thus reveal differential metabolic sensitivity of TORC1- and Ilp-dependent growth and suggest that cell-autonomous metabolic defects might elicit local compensatory pathways. Conversely, enzyme knockdown in the whole organism results in animal death. Importantly, our study weakens the use of single inhibitors to fight mTOR-related diseases and strengthens the use of drug combination and selective tissue-targeting. 相似文献
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J Parcq T Bertrand A Montagne A F Baron R Macrez J M Billard A Briens Y Hommet J Wu M Yepes H R Lijnen P Dutar E Anglés-Cano D Vivien 《Cell death and differentiation》2012,19(12):1983-1991
Unlike other serine proteases that are zymogens, the single-chain form of tissue plasminogen activator (sc-tPA) exhibits an intrinsic activity similar to that of its cleaved two-chain form (tc-tPA), especially in the presence of fibrin. In the central nervous system tPA controls brain functions and dysfunctions through its proteolytic activity. We demonstrated here, both in vitro and in vivo, that the intrinsic activity of sc-tPA selectively modulates N-methyl-𝒟-aspartate receptor (NMDAR) signaling as compared with tc-tPA. Thus, sc-tPA enhances NMDAR-mediated calcium influx, Erk(½) activation and neurotoxicity in cultured cortical neurons, excitotoxicity in the striatum and NMDAR-dependent long-term potentiation in the hippocampal CA-1 network. As the first demonstration of a differential function for sc-tPA and tc-tPA, this finding opens a new area of investigations on tPA functions in the absence of its allosteric regulator, fibrin. 相似文献
68.
ALIX binds a YPX(3)L motif of the GPCR PAR1 and mediates ubiquitin-independent ESCRT-III/MVB sorting
Dores MR Chen B Lin H Soh UJ Paing MM Montagne WA Meerloo T Trejo J 《The Journal of cell biology》2012,197(3):407-419
The sorting of signaling receptors to lysosomes is an essential regulatory process in mammalian cells. During degradation, receptors are modified with ubiquitin and sorted by endosomal sorting complex required for transport (ESCRT)-0, -I, -II, and -III complexes into intraluminal vesicles (ILVs) of multivesicular bodies (MVBs). However, it remains unclear whether a single universal mechanism mediates MVB sorting of all receptors. We previously showed that protease-activated receptor 1 (PAR1), a G protein-coupled receptor (GPCR) for thrombin, is internalized after activation and sorted to lysosomes independent of ubiquitination and the ubiquitin-binding ESCRT components hepatocyte growth factor-regulated tyrosine kinase substrate and Tsg101. In this paper, we report that PAR1 sorted to ILVs of MVBs through an ESCRT-III-dependent pathway independent of ubiquitination. We further demonstrate that ALIX, a charged MVB protein 4-ESCRT-III interacting protein, bound to a YPX(3)L motif of PAR1 via its central V domain to mediate lysosomal degradation. This study reveals a novel MVB/lysosomal sorting pathway for signaling receptors that bypasses the requirement for ubiquitination and ubiquitin-binding ESCRTs and may be applicable to a subset of GPCRs containing YPX(n)L motifs. 相似文献
69.
Background
Species are fundamental units in biology, yet much debate exists surrounding how we should delineate species in nature. Species discovery now requires the use of separate, corroborating datasets to quantify independently evolving lineages and test species criteria. However, the complexity of the speciation process has ushered in a need to infuse studies with new tools capable of aiding in species delineation. We suggest that model-based assignment tests are one such tool. This method circumvents constraints with traditional population genetic analyses and provides a novel means of describing cryptic and complex diversity in natural systems. Using toad-headed agamas of the Phrynocephalus vlangalii complex as a case study, we apply model-based assignment tests to microsatellite DNA data to test whether P. putjatia, a controversial species that closely resembles P. vlangalii morphologically, represents a valid species. Mitochondrial DNA and geographic data are also included to corroborate the assignment test results. 相似文献70.
Corry-Anke Brandsma Machteld N Hylkema Barry WA van der Strate Dirk-Jan Slebos Marjan A Luinge Marie Geerlings Wim Timens Dirkje S Postma Huib AM Kerstjens 《Respiratory research》2008,9(1):17