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121.
Activity-regulated N-cadherin endocytosis 总被引:3,自引:0,他引:3
Enduring forms of synaptic plasticity are thought to require ongoing regulation of adhesion molecules, such as N-cadherin, at synaptic junctions. Little is known about the activity-regulated trafficking of adhesion molecules. Here we demonstrate that surface N-cadherin undergoes a surprisingly high basal rate of internalization. Upon activation of NMDA receptors (NMDAR), the rate of N-cadherin endocytosis is significantly reduced, resulting in an accumulation of N-cadherin in the plasma membrane. Beta-catenin, an N-cadherin binding partner, is a primary regulator of N-cadherin endocytosis. Following NMDAR stimulation, beta-catenin accumulates in spines and exhibits increased binding to N-cadherin. Overexpression of a mutant form of beta-catenin, Y654F, prevents the NMDAR-dependent regulation of N-cadherin internalization, resulting in stabilization of surface N-cadherin molecules. Furthermore, the stabilization of surface N-cadherin blocks NMDAR-dependent synaptic plasticity. These results indicate that NMDAR activity regulates N-cadherin endocytosis, providing a mechanistic link between structural plasticity and persistent changes in synaptic efficacy. 相似文献
122.
Community dynamics and heterogeneities in mixed bacterial communities subjected to nutrient periodicities 总被引:2,自引:0,他引:2
Sixteen replicate microcosms were inoculated with a mixed assemblage of heterotrophic bacteria and provided with discrete pulses of protein as carbon and energy source. The dynamics of community structure were monitored by 16S rRNA gene polymerase chain reaction denaturant gradient gel electrophoresis (PCR-DGGE). The results were consistent with a strong role for biological interactions in maintaining diversity. Replicate microcosms developed different microbial communities. For systems exposed to nutrient pulses every 7 days, the number of DGGE bands averaged 13 +/- 4 (mean +/- SD) and the Dice similarity coefficient between pairs ranged from 0.08 to 0.67. In each of 16 systems provided protein once each day, there were dynamic changes over the first 30 days but community composition was stable over the next 20 days. However, most systems differed from each other; two-thirds of the pairwise comparisons had similarity coefficients in the range of 0.35-0.63. These 16 systems contained 10 +/- 2 phylotypes (mean +/- SD) and in aggregate 34 phylotypes were found in the 16 systems. Most phylotypes were found in < 25% of the systems, and there were not strong networks of association among phylotypes. 相似文献
123.
Ricardo Saban Michael R D'Andrea Patricia Andrade-Gordon Claudia K Derian Igor Dozmorov Michael A Ihnat Robert E Hurst Carole A Davis Cindy Simpson Marcia R Saban 《BMC physiology》2007,7(1):4
Background
In general, inflammation plays a role in most bladder pathologies and represents a defense reaction to injury that often times is two edged. In particular, bladder neurogenic inflammation involves the participation of mast cells and sensory nerves. Increased mast cell numbers and tryptase release represent one of the prevalent etiologic theories for interstitial cystitis and other urinary bladder inflammatory conditions. The activity of mast cell-derived tryptase as well as thrombin is significantly increased during inflammation. Those enzymes activate specific G-protein coupled proteinase-activated receptors (PAR)s. 相似文献124.
Boots AM Hubers H Kouwijzer M den Hoed-van Zandbrink L Westrek-Esselink BM van Doorn C Stenger R Bos ES van Lierop MJ Verheijden GF Timmers CM van Staveren CJ 《Arthritis research & therapy》2007,9(4):R71
We sought to identify an altered peptide ligand (APL) based on the endogenously expressed synovial auto-epitope of human cartilage glycoprotein-39 (HC gp-39) for modulation of cognate, HLA-DR4-restricted T cells. For this purpose we employed a panel of well-characterized T cell hybridomas generated from HC gp-39-immunized HLA-DR4 transgenic mice. The hybridomas all respond to the HC gp-39(263-275) epitope when bound to HLA-DR4(B1*0401) but differ in their fine specificities. First, the major histocompatibility complex (MHC) and T-cell receptor (TCR) contact residues were identified by analysis of single site substituted analogue peptides for HLA-DR4 binding and cognate T cell recognition using both T hybridomas and polyclonal T cells from peptide-immunized HLA-DR4 transgenic mice. Analysis of single site substituted APL by cognate T cells led to identification of Phe265 as the dominant MHC anchor. The amino acids Ala268, Ser269, Glu271 and Thr272 constituted the major TCR contact residues, as substitution at these positions did not affect HLA-DR4(B1*0401) binding but abrogated T cell responses. A structural model for visualisation of TCR recognition was derived. Second, a set of non-classical APLs, modified at the MHC key anchor position but with unaltered TCR contacts, was developed. When these APLs were analysed, a partial TCR agonist was identified and found to modulate the HC gp-39(263-275)-specific, pro-inflammatory response in HLA-DR4 transgenic mice. We identified a non-classical APL by modification of the p1 MHC anchor in a synovial auto-epitope. This APL may qualify for rheumatoid arthritis immunotherapy. 相似文献
125.
Masoud Zamani Esteki Eftychia Dimitriadou Ligia Mateiu Cindy Melotte Niels Van der Aa Parveen Kumar Rakhi Das Koen Theunis Jiqiu Cheng Eric Legius Yves Moreau Sophie Debrock Thomas D’Hooghe Pieter Verdyck Martine De Rycke Karen Sermon Joris R. Vermeesch Thierry Voet 《American journal of human genetics》2015,96(6):894-912
Methods for haplotyping and DNA copy-number typing of single cells are paramount for studying genomic heterogeneity and enabling genetic diagnosis. Before analyzing the DNA of a single cell by microarray or next-generation sequencing, a whole-genome amplification (WGA) process is required, but it substantially distorts the frequency and composition of the cell’s alleles. As a consequence, haplotyping methods suffer from error-prone discrete SNP genotypes (AA, AB, BB) and DNA copy-number profiling remains difficult because true DNA copy-number aberrations have to be discriminated from WGA artifacts. Here, we developed a single-cell genome analysis method that reconstructs genome-wide haplotype architectures as well as the copy-number and segregational origin of those haplotypes by employing phased parental genotypes and deciphering WGA-distorted SNP B-allele fractions via a process we coin haplarithmisis. We demonstrate that the method can be applied as a generic method for preimplantation genetic diagnosis on single cells biopsied from human embryos, enabling diagnosis of disease alleles genome wide as well as numerical and structural chromosomal anomalies. Moreover, meiotic segregation errors can be distinguished from mitotic ones. 相似文献
126.
Dimitra Gkika Loic Lemonnier George Shapovalov Dmitri Gordienko Céline Poux Michela Bernardini Alexandre Bokhobza Gabriel Bidaux Cindy Degerny Kathye Verreman Basma Guarmit Mohamed Benahmed Yvan de Launoit Rene J.M. Bindels Alessandra Fiorio Pla Natalia Prevarskaya 《The Journal of cell biology》2015,208(1):89-107
TRPM8 is a cold sensor that is highly expressed in the prostate as well as in other non-temperature-sensing organs, and is regulated by downstream receptor–activated signaling pathways. However, little is known about the intracellular proteins necessary for channel function. Here, we identify two previously unknown proteins, which we have named “TRP channel–associated factors” (TCAFs), as new TRPM8 partner proteins, and we demonstrate that they are necessary for channel function. TCAF1 and TCAF2 both bind to the TRPM8 channel and promote its trafficking to the cell surface. However, they exert opposing effects on TRPM8 gating properties. Functional interaction of TCAF1/TRPM8 also leads to a reduction in both the speed and directionality of migration of prostate cancer cells, which is consistent with an observed loss of expression of TCAF1 in metastatic human specimens, whereas TCAF2 promotes migration. The identification of TCAFs introduces a novel mechanism for modulation of TRPM8 channel activity. 相似文献
127.
Stephan Wilmes Oliver Beutel Zhi Li Véronique Francois-Newton Christian P. Richter Dennis Janning Cindy Kroll Patrizia Hanhart Katharina H?tte Changjiang You Gilles Uzé Sandra Pellegrini Jacob Piehler 《The Journal of cell biology》2015,209(4):579-593
Type I interferons (IFNs) activate differential cellular responses through a shared cell surface receptor composed of the two subunits, IFNAR1 and IFNAR2. We propose here a mechanistic model for how IFN receptor plasticity is regulated on the level of receptor dimerization. Quantitative single-molecule imaging of receptor assembly in the plasma membrane of living cells clearly identified IFN-induced dimerization of IFNAR1 and IFNAR2. The negative feedback regulator ubiquitin-specific protease 18 (USP18) potently interferes with the recruitment of IFNAR1 into the ternary complex, probably by impeding complex stabilization related to the associated Janus kinases. Thus, the responsiveness to IFNα2 is potently down-regulated after the first wave of gene induction, while IFNβ, due to its ∼100-fold higher binding affinity, is still able to efficiently recruit IFNAR1. Consistent with functional data, this novel regulatory mechanism at the level of receptor assembly explains how signaling by IFNβ is maintained over longer times compared with IFNα2 as a temporally encoded cause of functional receptor plasticity. 相似文献
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