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排序方式: 共有324条查询结果,搜索用时 15 毫秒
81.
Junt T Moseman EA Iannacone M Massberg S Lang PA Boes M Fink K Henrickson SE Shayakhmetov DM Di Paolo NC van Rooijen N Mempel TR Whelan SP von Andrian UH 《Nature》2007,450(7166):110-114
Lymph nodes prevent the systemic dissemination of pathogens such as viruses that infect peripheral tissues after penetrating the body's surface barriers. They are also the staging ground of adaptive immune responses to pathogen-derived antigens. It is unclear how virus particles are cleared from afferent lymph and presented to cognate B cells to induce antibody responses. Here we identify a population of CD11b+CD169+MHCII+ macrophages on the floor of the subcapsular sinus (SCS) and in the medulla of lymph nodes that capture viral particles within minutes after subcutaneous injection. Macrophages in the SCS translocated surface-bound viral particles across the SCS floor and presented them to migrating B cells in the underlying follicles. Selective depletion of these macrophages compromised local viral retention, exacerbated viraemia of the host, and impaired local B-cell activation. These findings indicate that CD169+ macrophages have a dual physiological function. They act as innate 'flypaper' by preventing the systemic spread of lymph-borne pathogens and as critical gatekeepers at the lymph-tissue interface that facilitate the recognition of particulate antigens by B cells and initiate humoral immune responses. 相似文献
82.
Mutations in GRIN2A and GRIN2B encoding regulatory subunits of NMDA receptors cause variable neurodevelopmental phenotypes 总被引:1,自引:0,他引:1
Endele S Rosenberger G Geider K Popp B Tamer C Stefanova I Milh M Kortüm F Fritsch A Pientka FK Hellenbroich Y Kalscheuer VM Kohlhase J Moog U Rappold G Rauch A Ropers HH von Spiczak S Tönnies H Villeneuve N Villard L Zabel B Zenker M Laube B Reis A Wieczorek D Van Maldergem L Kutsche K 《Nature genetics》2010,42(11):1021-1026
N-methyl-D-aspartate (NMDA) receptors mediate excitatory neurotransmission in the mammalian brain. Two glycine-binding NR1 subunits and two glutamate-binding NR2 subunits each form highly Ca2(+)-permeable cation channels which are blocked by extracellular Mg2(+) in a voltage-dependent manner. Either GRIN2B or GRIN2A, encoding the NMDA receptor subunits NR2B and NR2A, was found to be disrupted by chromosome translocation breakpoints in individuals with mental retardation and/or epilepsy. Sequencing of GRIN2B in 468 individuals with mental retardation revealed four de novo mutations: a frameshift, a missense and two splice-site mutations. In another cohort of 127 individuals with idiopathic epilepsy and/or mental retardation, we discovered a GRIN2A nonsense mutation in a three-generation family. In a girl with early-onset epileptic encephalopathy, we identified the de novo GRIN2A mutation c.1845C>A predicting the amino acid substitution p.N615K. Analysis of NR1-NR2A(N615K) (NR2A subunit with the p.N615K alteration) receptor currents revealed a loss of the Mg2(+) block and a decrease in Ca2(+) permeability. Our findings suggest that disturbances in the neuronal electrophysiological balance during development result in variable neurological phenotypes depending on which NR2 subunit of NMDA receptors is affected. 相似文献
83.
85.
Reboul J Vaglio P Rual JF Lamesch P Martinez M Armstrong CM Li S Jacotot L Bertin N Janky R Moore T Hudson JR Hartley JL Brasch MA Vandenhaute J Boulton S Endress GA Jenna S Chevet E Papasotiropoulos V Tolias PP Ptacek J Snyder M Huang R Chance MR Lee H Doucette-Stamm L Hill DE Vidal M 《Nature genetics》2003,34(1):35-41
To verify the genome annotation and to create a resource to functionally characterize the proteome, we attempted to Gateway-clone all predicted protein-encoding open reading frames (ORFs), or the 'ORFeome,' of Caenorhabditis elegans. We successfully cloned approximately 12,000 ORFs (ORFeome 1.1), of which roughly 4,000 correspond to genes that are untouched by any cDNA or expressed-sequence tag (EST). More than 50% of predicted genes needed corrections in their intron-exon structures. Notably, approximately 11,000 C. elegans proteins can now be expressed under many conditions and characterized using various high-throughput strategies, including large-scale interactome mapping. We suggest that similar ORFeome projects will be valuable for other organisms, including humans. 相似文献
86.
Pinyopich A Ditta GS Savidge B Liljegren SJ Baumann E Wisman E Yanofsky MF 《Nature》2003,424(6944):85-88
Carpels are essential for sexual plant reproduction because they house the ovules and subsequently develop into fruits that protect, nourish and ultimately disperse the seeds. The AGAMOUS (AG) gene is necessary for plant sexual reproduction because stamens and carpels are absent from ag mutant flowers. However, the fact that sepals are converted into carpelloid organs in certain mutant backgrounds even in the absence of AG activity indicates that an AG-independent carpel-development pathway exists. AG is a member of a monophyletic clade of MADS-box genes that includes SHATTERPROOF1 (SHP1), SHP2 and SEEDSTICK (STK), indicating that these four genes might share partly redundant activities. Here we show that the SHP genes are responsible for AG-independent carpel development. We also show that the STK gene is required for normal development of the funiculus, an umbilical-cord-like structure that connects the developing seed to the fruit, and for dispersal of the seeds when the fruit matures. We further show that all four members of the AG clade are required for specifying the identity of ovules, the landmark invention during the course of vascular plant evolution that enabled seed plants to become the most successful group of land plants. 相似文献
87.
Correction to: The role of connexin proteins and their channels in radiation-induced atherosclerosis
Ramadan Raghda Baatout Sarah Aerts An Leybaert Luc 《Cellular and molecular life sciences : CMLS》2021,78(10):4847-4847
Cellular and Molecular Life Sciences - A correction to this paper has been published: https://doi.org/10.1007/s00018-021-03811-z 相似文献
88.
Iman Azimi Alice H. Bong Greta X. H. Poo Kaela Armitage Dawn Lok Sarah J. Roberts-Thomson Gregory R. Monteith 《Cellular and molecular life sciences : CMLS》2018,75(24):4525-4537
Store-operated Ca2+ entry is a pathway that is remodelled in a variety of cancers, and altered expression of the components of store-operated Ca2+ entry is a feature of breast cancer cells of the basal molecular subtype. Studies of store-operated Ca2+ entry in breast cancer cells have used non-specific pharmacological inhibitors, complete depletion of intracellular Ca2+ stores and have mostly focused on MDA-MB-231 cells (a basal B breast cancer cell line). These studies compared the effects of the selective store-operated Ca2+ entry inhibitors Synta66 and YM58483 (also known as BTP2) on global cytosolic free Ca2+ ([Ca2+]CYT) changes induced by physiological stimuli in a different breast cancer basal cell line model, MDA-MB-468. The effects of these agents on proliferation as well as serum and epidermal growth factor (EGF) induced migration were also assessed. Activation with the purinergic receptor activator adenosine triphosphate, produced a sustained increase in [Ca2+]CYT that was entirely dependent on store-operated Ca2+ entry. The protease activated receptor 2 activator, trypsin, and EGF also produced Ca2+ influx that was sensitive to both Synta66 and YM58483. Serum-activated migration of MDA-MB-468 breast cancer cells was sensitive to both store-operated Ca2+ inhibitors. However, proliferation and EGF-activated migration was differentially affected by Synta66 and YM58483. These studies highlight the need to define the exact mechanisms of action of different store-operated calcium entry inhibitors and the impact of such differences in the control of tumour progression pathways. 相似文献
89.
Albert Lee Stephanie L. Rayner Serene S. L. Gwee Alana De Luca Hamideh Shahheydari Vinod Sundaramoorthy Audrey Ragagnin Marco Morsch Rowan Radford Jasmin Galper Sarah Freckleton Bingyang Shi Adam K. Walker Emily K. Don Nicholas J. Cole Shu Yang Kelly L. Williams Justin J. Yerbury Ian P. Blair Julie D. Atkin Mark P. Molloy Roger S. Chung 《Cellular and molecular life sciences : CMLS》2018,75(2):335-354
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are fatal neurodegenerative disorders that have common molecular and pathogenic characteristics, such as aberrant accumulation and ubiquitylation of TDP-43; however, the mechanisms that drive this process remain poorly understood. We have recently identified CCNF mutations in familial and sporadic ALS and FTD patients. CCNF encodes cyclin F, a component of an E3 ubiquitin–protein ligase (SCFcyclin F) complex that is responsible for ubiquitylating proteins for degradation by the ubiquitin–proteasome system. In this study, we examined the ALS/FTD-causing p.Ser621Gly (p.S621G) mutation in cyclin F and its effect upon downstream Lys48-specific ubiquitylation in transfected Neuro-2A and SH-SY5Y cells. Expression of mutant cyclin FS621G caused increased Lys48-specific ubiquitylation of proteins in neuronal cells compared to cyclin FWT. Proteomic analysis of immunoprecipitated Lys48-ubiquitylated proteins from mutant cyclin FS621G-expressing cells identified proteins that clustered within the autophagy pathway, including sequestosome-1 (p62/SQSTM1), heat shock proteins, and chaperonin complex components. Examination of autophagy markers p62, LC3, and lysosome-associated membrane protein 2 (Lamp2) in cells expressing mutant cyclin FS621G revealed defects in the autophagy pathway specifically resulting in impairment in autophagosomal–lysosome fusion. This finding highlights a potential mechanism by which cyclin F interacts with p62, the receptor responsible for transporting ubiquitylated substrates for autophagic degradation. These findings demonstrate that ALS/FTD-causing mutant cyclin FS621G disrupts Lys48-specific ubiquitylation, leading to accumulation of substrates and defects in the autophagic machinery. This study also demonstrates that a single missense mutation in cyclin F causes hyper-ubiquitylation of proteins that can indirectly impair the autophagy degradation pathway, which is implicated in ALS pathogenesis. 相似文献
90.
Anske Van den Abbeele Sarah De Clercq Ariane De Ganck Veerle De Corte Berlinda Van Loo Sameh Hamdy Soror Vasundara Srinivasan Jan Steyaert Joël Vandekerckhove Jan Gettemans 《Cellular and molecular life sciences : CMLS》2010,67(9):1519-1535
RNA interference has tremendously advanced our understanding of gene function but recent reports have exposed undesirable
side-effects. Recombinant Camelid single-domain antibodies (VHHs) provide an attractive means for studying protein function without affecting gene expression.
We raised VHHs against gelsolin (GsnVHHs), a multifunctional actin-binding protein that controls cellular actin organization
and migration. GsnVHH-induced delocalization of gelsolin to mitochondria or the nucleus in mammalian cells reveals distinct
subpopulations including free gelsolin and actin-bound gelsolin complexes. GsnVHH 13 specifically recognizes Ca2+-activated gelsolin (K
d ~10 nM) while GsnVHH 11 binds gelsolin irrespective of Ca2+ (K
d ~5 nM) but completely blocks its interaction with G-actin. Both GsnVHHs trace gelsolin in membrane ruffles of EGF-stimulated
MCF-7 cells and delay cell migration without affecting F-actin severing/capping or actin nucleation activities by gelsolin.
We conclude that VHHs represent a potent way of blocking structural proteins and that actin nucleation by gelsolin is more
complex than previously anticipated. 相似文献