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31.
32.
J G Grossmann M Neu E Pantos F J Schwab R W Evans E Townes-Andrews P F Lindley H Appel W G Thies S S Hasnain 《Journal of molecular biology》1992,225(3):811-819
X-ray solution scattering has been used for studying the structural changes that take place upon uptake and release of iron from serum and chicken ovo-transferrin and human lactoferrin. In the case of chicken ovo-transferrin, data have been obtained for both the intact protein and the isolated N and C-lobes with and without iron. These studies reveal that both lobes undergo a change that is consistent with an opening of the inter-domain cleft when iron is removed from the protein. We suggest that the conformational change of the protein increases the specificity of receptor binding and that the closed configuration of the iron-loaded protein is one, or perhaps the, decisive step in the mechanism for receptor-mediated endocytosis. 相似文献
33.
Juxing Chen Jinzhi Wang Kathrin R. Meyers Caroline A. Enns 《Traffic (Copenhagen, Denmark)》2009,10(10):1488-1501
Transferrin receptor 2 (TfR2) is a homologue of transferrin receptor 1 (TfR1) but has distinct functions from TfR1 in iron homeostasis. In keeping with its proposed role in iron sensing, previous studies showed that TfR2 has a short half-life and that holo-Tf stabilizes TfR2 by redirecting it from a degradative pathway to a recycling pathway. In this study, we characterized how the endocytosis, recycling and degradation of TfR2 relates to its function and differs from TfR1. TfR2 endocytosis was adaptor protein-2 (AP-2) dependent. Flow cytometry analysis showed that TfR1 and TfR2 utilized the same endocytic pathway only in the presence of holo-Tf, indicating that holo-Tf alters the interaction of TfR2 with the endocytic machinery. Unlike TfR1, phosphofurin acidic cluster sorting protein 1 (PACS-1) binds to the cytoplasmic domain of TfR2 and data suggest that PACS-1 is involved in the TfR2 recycling. Depletion of TSG101 by siRNA or expression of a dominant negative Vps4 inhibited TfR2 degradation, indicating that TfR2 degradation occurs through a multivesicular body (MVB) pathway. TfR2 degradation is not mediated through ubiquitination on the single lysine (K31) in the cytoplasmic domain or on the amino terminal residue. No ubiquitination of TfR2 by HA-ubiquitin was detected, indicating a lack of direct TfR2 ubiquitination involvement in its degradation. 相似文献
34.
Synaptic destabilization by neuronal Nogo-A 总被引:1,自引:0,他引:1
Aloy EM Weinmann O Pot C Kasper H Dodd DA Rülicke T Rossi F Schwab ME 《Brain Cell Biology》2006,35(2-3):137-157
Formation and maintenance of a neuronal network is based on a balance between plasticity and stability of synaptic connections.
Several molecules have been found to regulate the maintenance of excitatory synapses but nothing is known about the molecular
mechanisms involved in synaptic stabilization versus disassembly at inhibitory synapses. Here, we demonstrate that Nogo-A,
which is well known to be present in myelin and inhibit growth in the adult CNS, is present in inhibitory presynaptic terminals
in cerebellar Purkinje cells at the time of Purkinje cell-Deep Cerebellar Nuclei (DCN) inhibitory synapse formation and is
then downregulated during synapse maturation. We addressed the role of neuronal Nogo-A in synapse maturation by generating
several mouse lines overexpressing Nogo-A, starting at postnatal ages and throughout adult life, specifically in cerebellar
Purkinje cells and their terminals. The overexpression of Nogo-A induced a progressive disassembly, retraction and loss of
the inhibitory Purkinje cell terminals. This led to deficits in motor learning and coordination in the transgenic mice. Prior
to synapse disassembly, the overexpression of neuronal Nogo-A led to the downregulation of the synaptic scaffold proteins
spectrin, spectrin-E and β-catenin in the postsynaptic neurons. Our data suggest that neuronal Nogo-A might play a role in
the maintenance of inhibitory synapses by modulating the expression of synaptic anchoring molecules.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献
35.
Petitdemange C Becquart P Wauquier N Béziat V Debré P Leroy EM Vieillard V 《PLoS pathogens》2011,7(9):e1002268
Chikungunya virus (CHIKV) is a worldwide emerging pathogen. In humans it causes a syndrome characterized by high fever, polyarthritis, and in some cases lethal encephalitis. Growing evidence indicates that the innate immune response plays a role in controlling CHIKV infection. We show here that CHIKV induces major but transient modifications in NK-cell phenotype and function soon after the onset of acute infection. We report a transient clonal expansion of NK cells that coexpress CD94/NKG2C and inhibitory receptors for HLA-C1 alleles and are correlated with the viral load. Functional tests reveal cytolytic capacity driven by NK cells in the absence of exogenous signals and severely impaired IFN-γ production. Collectively these data provide insight into the role of this unique subset of NK cells in controlling CHIKV infection by subset-specific expansion in response to acute infection, followed by a contraction phase after viral clearance. 相似文献
36.
Caroline J. Rose Katrin Hammerschmidt Yuriy Pichugin Paul B. Rainey 《Ecology letters》2020,23(9):1380-1390
The evolutionary transition to multicellularity has occurred on numerous occasions, but transitions to complex life forms are rare. Here, using experimental bacterial populations as proxies for nascent multicellular organisms, we manipulate ecological factors shaping the evolution of groups. Groups were propagated under regimes requiring reproduction via a life cycle replete with developmental and dispersal (propagule) phases, but in one treatment lineages never mixed, whereas in a second treatment, cells from different lineages experienced intense competition during the dispersal phase. The latter treatment favoured traits promoting cell growth at the expense of traits underlying group fitness – a finding that is supported by results from a mathematical model. Our results show that the transition to multicellularity benefits from ecological conditions that maintain discreteness not just of the group (soma) phase, but also of the dispersal (germline) phase. 相似文献
37.
Nasi Mian Caroline E. Anderson Andrew J. Pope Anthony R. Smith Paul S. Richardson Kim Balfre Paul W. Kent 《The Biochemical journal》1982,208(2):425-433
Chicken tracheal mucosa in vitro transported and incorporated radioactive precursors into mucins, which were secreted at a steady rate into the tracheal lumen. Secretion of mucins labelled with 35S and 3H after pulse-labelling of the mucosal layer with Na235SO4 and d-[1-3H]glucosamine as precursors was an energy-dependent process, as it was strongly inhibited by the action of respiratory-chain inhibitors, an uncoupler of oxidative phosphorylation, a metabolic blocker and a temperature shift from 41°C to 5°C. On the other hand, both cholinergic and parasympathomimetic agents considerably increased the secretion of dual-radiolabelled mucins when applied on the submucosal side of the trachea. The effect of Ca2+ was directional, since only high submucosal (3.6 or 18mm) or low luminal (zero or 0.18mm) Ca2+ massively enhanced the secretion of radiolabelled mucin compared with the mucin output measured under physiological Ca2+ conditions (1.8mm). Whereas application of ionophore A23187 on either side of the trachea significantly increased mucin output, its presence in the appropriate tracheal compartment and under appropriate Ca2+ conditions further accentuated the output of radiolabelled mucins. Addition of acetylcholine under appropriate conditions also had an additive effect on the Ca2+-stimulated secretion of mucins. Ca2+ stimulation of mucin secretion appears to be dependent on the metabolic integrity of the mucosal cells. Mucins secreted in response to high submucosal and low luminal [Ca2+] appear to consist of a number of different types of glycoproteins, as judged from their ion-exchange-chromatographic behaviour. 相似文献
38.
Genetic and environmental influences on migraine: a twin study across six countries. 总被引:7,自引:0,他引:7
Elles J Mulder Caroline Van Baal David Gaist Mikko Kallela Jaakko Kaprio Dan A Svensson Dale R Nyholt Nicholas G Martin Alex J MacGregor Lynn F Cherkas Dorret I Boomsma Aarno Palotie 《Twin research》2003,6(5):422-431
Migraine is a common neurovascular brain disorder that is manifested in recurrent episodes of disabling headache. The aim of the present study was to compare the prevalence and heritability of migraine across six of the countries that participate in GenomEUtwin project including a total number of 29,717 twin pairs. Migraine was assessed by questionnaires that differed between most countries. It was most prevalent in Danish and Dutch females (32% and 34%, respectively), whereas the lowest prevalence was found in the younger and older Finnish cohorts (13% and 10%, respectively). The estimated genetic variance (heritability) was significant and the same between sexes in all countries. Heritability ranged from 34% to 57%, with lowest estimates in Australia, and highest estimates in the older cohort of Finland, the Netherlands, and Denmark. There was some indication that part of the genetic variance was non-additive, but this was significant in Sweden only. In addition to genetic factors, environmental effects that are non-shared between members of a twin pair contributed to the liability of migraine. After migraine definitions are homogenized among the participating countries, the GenomEUtwin project will provide a powerful resource to identify the genes involved in migraine. 相似文献
39.
Maunoury F Berveiller D Lelarge C Pontailler JY Vanbostal L Damesin C 《Oecologia》2007,151(2):268-279
The stable C isotope composition (δ13C) of CO2 respired by trunks was examined in a mature temperate deciduous oak forest (Quercus petraea). Month-to-month, day-to-day and diurnal, measurements were made to determine the range of variations at different temporal
scales. Trunk growth and respiration rates were assessed. Phloem tissue was sampled and was analysed for total organic matter
and soluble sugar 13C composition. The CO2 respired by trunk was always enriched in 13C relative to the total organic matter, sometimes by as much as 5‰. The δ13C of respired CO2 exhibited a large seasonal variation (3.3‰), with a relative maximum at the beginning of the growth period. The lowest values
occurred in summer when the respiration rates were maximal. After the cessation of radial trunk growth, the respired CO2 δ13C values showed a progressive increase, which was linked to a parallel increase in soluble sugar content in the phloem tissue
(R = 0.95; P < 0.01). At the same time, the respiration rates declined. This limited use of the substrate pool might allow the discrimination
during respiration to be more strongly expressed. The late-season increase in CO2 δ13C might also be linked to a shift from recently assimilated C to reserves. At the seasonal scale, CO2 δ13C was negatively correlated with air temperature (R = −0.80; P < 0.01). The diurnal variation sometimes reached 3‰, but the range and the pattern depended on the period within the growing
season. Contrary to expectations, diurnal variations were maximal in winter and spring when the leaves were missing or not
totally functional. By contrast to the seasonal scale, these diurnal variations were not related to air temperature or sugar
content. Our study shows that seasonal and diurnal variations of respired 13C exhibited a similar large range but were probably explained by different mechanisms. 相似文献
40.
Hernandez-Pigeon H Jean C Charruyer A Haure MJ Titeux M Tonasso L Quillet-Mary A Baudouin C Charveron M Laurent G 《The Journal of biological chemistry》2006,281(19):13525-13532
Ultraviolet (UV) radiation from the sun is widely considered as a major cause of human skin photoaging and skin cancer. Granzyme B (GrB) and perforin (PFN) are two proteins contained in granules and implicated in one of the mechanisms by which cytotoxic lymphocytes and natural killer cells exert their cytotoxicity against virus-infected, alloreactive, or transformed cells. The distribution of GrB and PFN in the skin has received little attention. However, Berthou and co-workers (Berthou, C., Michel, L., Soulie, A., Jean-Louis, F., Flageul, B., Dubertret, L., Sigaux, F., Zhang, Y., and Sasportes, M. (1997) J. Immunol. 159, 5293-5300) described that, whereas freshly isolated epidermal cells did not express GrB or PFN, keratinocyte growth to confluence was associated with GrB and PFN mRNA and protein synthesis. In this work, we have investigated the possible role of UV-B on GrB and PFN expression in keratinocytes. We found that UV-B induces GrB and PFN expression in these cells through redox-, epidermal growth factor receptor-, and mitogen-activated protein kinase-dependent signaling. Furthermore, under UV irradiation, keratinocytes acquire a significant cytotoxicity, which is GrB and PFN dependent, toward a variety of cellular targets including transformed T-lymphocytes, melanocytes, and keratinocytes. This phenomenon may have important functional consequences in the regulation of skin inflammatory response and in the emergence of cancer skin. 相似文献