排序方式: 共有63条查询结果,搜索用时 46 毫秒
31.
32.
Stéphanie?Jouannet Julien?Saint-Pol Laurent?Fernandez Viet?Nguyen Stéphanie?Charrin Claude?Boucheix Christel?Brou Pierre-Emmanuel?Milhiet Eric?RubinsteinEmail author 《Cellular and molecular life sciences : CMLS》2016,73(9):1895-1915
The metalloprotease ADAM10 mediates the shedding of the ectodomain of various cell membrane proteins, including APP, the precursor of the amyloid peptide Aβ, and Notch receptors following ligand binding. ADAM10 associates with the members of an evolutionary conserved subgroup of tetraspanins, referred to as TspanC8, which regulate its exit from the endoplasmic reticulum. Here we show that 4 of these TspanC8 (Tspan5, Tspan14, Tspan15 and Tspan33) which positively regulate ADAM10 surface expression levels differentially impact ADAM10-dependent Notch activation and the cleavage of several ADAM10 substrates, including APP, N-cadherin and CD44. Sucrose gradient fractionation, single molecule tracking and quantitative mass-spectrometry analysis of the repertoire of molecules co-immunoprecipitated with Tspan5, Tspan15 and ADAM10 show that these two tetraspanins differentially regulate ADAM10 membrane compartmentalization. These data represent a unique example where several tetraspanins differentially regulate the function of a common partner protein through a distinct membrane compartmentalization. 相似文献
33.
Aitman TJ Critser JK Cuppen E Dominiczak A Fernandez-Suarez XM Flint J Gauguier D Geurts AM Gould M Harris PC Holmdahl R Hubner N Izsvák Z Jacob HJ Kuramoto T Kwitek AE Marrone A Mashimo T Moreno C Mullins J Mullins L Olsson T Pravenec M Riley L Saar K Serikawa T Shull JD Szpirer C Twigger SN Voigt B Worley K 《Nature genetics》2008,40(5):516-522
The rat is an important system for modeling human disease. Four years ago, the rich 150-year history of rat research was transformed by the sequencing of the rat genome, ushering in an era of exceptional opportunity for identifying genes and pathways underlying disease phenotypes. Genome-wide association studies in human populations have recently provided a direct approach for finding robust genetic associations in common diseases, but identifying the precise genes and their mechanisms of action remains problematic. In the context of significant progress in rat genomic resources over the past decade, we outline achievements in rat gene discovery to date, show how these findings have been translated to human disease, and document an increasing pace of discovery of new disease genes, pathways and mechanisms. Finally, we present a set of principles that justify continuing and strengthening genetic studies in the rat model, and further development of genomic infrastructure for rat research. 相似文献
34.
MA Deardorff M Bando R Nakato E Watrin T Itoh M Minamino K Saitoh M Komata Y Katou D Clark KE Cole E De Baere C Decroos N Di Donato S Ernst LJ Francey Y Gyftodimou K Hirashima M Hullings Y Ishikawa C Jaulin M Kaur T Kiyono PM Lombardi L Magnaghi-Jaulin GR Mortier N Nozaki MB Petersen H Seimiya VM Siu Y Suzuki K Takagaki JJ Wilde PJ Willems C Prigent G Gillessen-Kaesbach DW Christianson FJ Kaiser LG Jackson T Hirota ID Krantz K Shirahige 《Nature》2012,489(7415):313-317
35.
Changes in plant community composition lag behind climate warming in lowland forests 总被引:2,自引:0,他引:2
Bertrand R Lenoir J Piedallu C Riofrío-Dillon G de Ruffray P Vidal C Pierrat JC Gégout JC 《Nature》2011,479(7374):517-520
Climate change is driving latitudinal and altitudinal shifts in species distribution worldwide, leading to novel species assemblages. Lags between these biotic responses and contemporary climate changes have been reported for plants and animals. Theoretically, the magnitude of these lags should be greatest in lowland areas, where the velocity of climate change is expected to be much greater than that in highland areas. We compared temperature trends to temperatures reconstructed from plant assemblages (observed in 76,634 surveys) over a 44-year period in France (1965-2008). Here we report that forest plant communities had responded to 0.54 °C of the effective increase of 1.07 °C in highland areas (500-2,600 m above sea level), while they had responded to only 0.02 °C of the 1.11 °C warming trend in lowland areas. There was a larger temperature lag (by 3.1 times) between the climate and plant community composition in lowland forests than in highland forests. The explanation of such disparity lies in the following properties of lowland, as compared to highland, forests: the higher proportion of species with greater ability for local persistence as the climate warms, the reduced opportunity for short-distance escapes, and the greater habitat fragmentation. Although mountains are currently considered to be among the ecosystems most threatened by climate change (owing to mountaintop extinction), the current inertia of plant communities in lowland forests should also be noted, as it could lead to lowland biotic attrition. 相似文献
36.
37.
R Truhaut J R Claude J M Warnet A Jacqueson A Piriou 《Comptes rendus des séances de l'Académie des sciences. Série D, Sciences naturelles》1978,286(6):493-497
The possible induction of fatty liver by Rifampicin has been investigated by oral administration of two different doses (200 and 400 mg/kg/24 h) of this antibiotic for a period of 8 days to male and female Rats. The results obtained are more constant and more coherent in male than in female. It is the 400 mg/kg/24 h dose which is more effective, leading to an increase of lipids, triglycerides and cholesterol in the liver and a decrease of serum triglycerides. A dose-effect relationship may exist. These preliminary data lead us to believe that Rifampicin may inhibit the synthesis of the protein moiety of lipoproteins, such as alpha-Amanitin, which is also a RNA-polymerase inhibitor. 相似文献
38.
Mutations in a Sar1 GTPase of COPII vesicles are associated with lipid absorption disorders 总被引:10,自引:0,他引:10
Jones B Jones EL Bonney SA Patel HN Mensenkamp AR Eichenbaum-Voline S Rudling M Myrdal U Annesi G Naik S Meadows N Quattrone A Islam SA Naoumova RP Angelin B Infante R Levy E Roy CC Freemont PS Scott J Shoulders CC 《Nature genetics》2003,34(1):29-31
Dietary fat is an important source of nutrition. Here we identify eight mutations in SARA2 that are associated with three severe disorders of fat malabsorption. The Sar1 family of proteins initiates the intracellular transport of proteins in COPII (coat protein)-coated vesicles. Our data suggest that chylomicrons, which vastly exceed the size of typical COPII vesicles, are selectively recruited by the COPII machinery for transport through the secretory pathways of the cell. 相似文献
39.
Mutations in IRF6 cause Van der Woude and popliteal pterygium syndromes 总被引:25,自引:0,他引:25
Kondo S Schutte BC Richardson RJ Bjork BC Knight AS Watanabe Y Howard E de Lima RL Daack-Hirsch S Sander A McDonald-McGinn DM Zackai EH Lammer EJ Aylsworth AS Ardinger HH Lidral AC Pober BR Moreno L Arcos-Burgos M Valencia C Houdayer C Bahuau M Moretti-Ferreira D Richieri-Costa A Dixon MJ Murray JC 《Nature genetics》2002,32(2):285-289
40.
The K-Cl cotransporter KCC3 is mutant in a severe peripheral neuropathy associated with agenesis of the corpus callosum 总被引:4,自引:0,他引:4
Howard HC Mount DB Rochefort D Byun N Dupré N Lu J Fan X Song L Rivière JB Prévost C Horst J Simonati A Lemcke B Welch R England R Zhan FQ Mercado A Siesser WB George AL McDonald MP Bouchard JP Mathieu J Delpire E Rouleau GA 《Nature genetics》2002,32(3):384-392
Peripheral neuropathy associated with agenesis of the corpus callosum (ACCPN) is a severe sensorimotor neuropathy associated with mental retardation, dysmorphic features and complete or partial agenesis of the corpus callosum. ACCPN is transmitted in an autosomal recessive fashion and is found at a high frequency in the province of Quebec, Canada. ACCPN has been previously mapped to chromosome 15q. The gene SLC12A6 (solute carrier family 12, member 6), which encodes the K+-Cl- transporter KCC3 and maps within the ACCPN candidate region, was screened for mutations in individuals with ACCPN. Four distinct protein-truncating mutations were found: two in the French Canadian population and two in non-French Canadian families. The functional consequence of the predominant French Canadian mutation (2436delG, Thr813fsX813) was examined by heterologous expression of wildtype and mutant KCC3 in Xenopus laevis oocytes; the truncated mutant is appropriately glycosylated and expressed at the cellular membrane, where it is non-functional. Mice generated with a targeted deletion of Slc12a6 have a locomotor deficit, peripheral neuropathy and a sensorimotor gating deficit, similar to the human disease. Our findings identify mutations in SLC12A6 as the genetic lesion underlying ACCPN and suggest a critical role for SLC12A6 in the development and maintenance of the nervous system. 相似文献