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排序方式: 共有163条查询结果,搜索用时 46 毫秒
91.
The SAC1 domain in synaptojanin is required for autophagosome maturation at presynaptic terminals
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Roeland Vanhauwaert Sabine Kuenen Roy Masius Adekunle Bademosi Julia Manetsberger Nils Schoovaerts Laura Bounti Serguei Gontcharenko Jef Swerts Sven Vilain Marina Picillo Paolo Barone Shashini T Munshi Femke MS de Vrij Steven A Kushner Natalia V Gounko Wim Mandemakers Vincenzo Bonifati Frederic A Meunier Sandra‐Fausia Soukup Patrik Verstreken 《The EMBO journal》2017,36(10):1392-1411
Presynaptic terminals are metabolically active and accrue damage through continuous vesicle cycling. How synapses locally regulate protein homeostasis is poorly understood. We show that the presynaptic lipid phosphatase synaptojanin is required for macroautophagy, and this role is inhibited by the Parkinson's disease mutation R258Q. Synaptojanin drives synaptic endocytosis by dephosphorylating PI(4,5)P2, but this function appears normal in SynaptojaninRQ knock‐in flies. Instead, R258Q affects the synaptojanin SAC1 domain that dephosphorylates PI(3)P and PI(3,5)P2, two lipids found in autophagosomal membranes. Using advanced imaging, we show that SynaptojaninRQ mutants accumulate the PI(3)P/PI(3,5)P2‐binding protein Atg18a on nascent synaptic autophagosomes, blocking autophagosome maturation at fly synapses and in neurites of human patient induced pluripotent stem cell‐derived neurons. Additionally, we observe neurodegeneration, including dopaminergic neuron loss, in SynaptojaninRQ flies. Thus, synaptojanin is essential for macroautophagy within presynaptic terminals, coupling protein turnover with synaptic vesicle cycling and linking presynaptic‐specific autophagy defects to Parkinson's disease. 相似文献
92.
G Rhys Williams MS 《BMC neurology》2001,1(1):2-6
Background and Purpose
Stroke, increasingly referred to as a "brain attack", is one of the leading causes of death and the leading cause of adult disability in the United States. It has recently been estimated that there were three quarters of a million strokes in the United States in 1995. The aim of this study was to replicate the 1995 estimate and examine if there was an increase from 1995 to 1996 by using a large administrative claims database representative of all 1996 US inpatient discharges. 相似文献93.
Estrella Klinzing MS Pechenik JA 《Journal of experimental marine biology and ecology》2000,252(2):255-279
Disproportionately large feeding structures have been used to infer food limitation in some marine invertebrate larvae, but few studies have investigated whether other factors alter larval morphology in similar ways. In this study, larvae of Crepidula fornicata were reared either at five different food concentrations of Isochrysis galbana (clone T-ISO) at a single temperature (22 degrees C) (Experiments I and II); or on three different phytoplankton species (Isochrysis galbana, Dunaliella tertiolecta, and Pavlova lutheri) at both high and low concentrations at a single temperature (22 degrees C) (Experiment III); or at high and low concentrations of Isochrysis galbana at four different temperatures between 16 and 25 degrees C (Experiment IV). Shell lengths and velar lobe dimensions were determined for individual larvae at intervals to monitor relative rates of velar and shell growth. In addition (Experiment V), fast growing and slow growing larvae in Experiment I were examined separately to determine whether velar lobes developed at similar rates (relative to shell growth) for fast and slow growing larvae within individual cultures. In general, velar lobes grew significantly larger, relative to shell length, when larvae were reared at low food concentrations (P<0.0001); for larvae of similar shell length, the velar lobes of those fed 1x10(4) cells ml(-1) were on average 17.7% larger than those of larvae fed 18x10(4) cells ml(-1) of T-ISO. In contrast, larvae fed different phytoplankton species at equivalently high food concentrations did not differ in relative velum size (P=0.2666), even though shell growth rates differed significantly for larvae raised on the different diets, indicating substantial variation in food quality. We also found that relative rates of velum and shell growth differed among fast and slow growing individuals within treatments. Temperature had no significant effect on relative rates of velar and shell growth within the 16-25 degrees C range tested (P=0.121), but may have altered the relationship between food concentration and relative velar growth. These results indicate that dramatically reduced food concentration induces disproportionate growth in the velar lobes of C. fornicata, but that interpretation of data from field-collected individuals of this species will be made difficult by the potentially confounding effects of temperature, food quality, and differences in individual growth potential. Assessments of food limitation using morphological measurements for field-collected larvae will need to be supplemented with other indicators before convincing conclusions about the extent of food limitation in C. fornicata can be drawn. 相似文献
94.
Wu CC Taylor RS Lane DR Ladinsky MS Weisz JA Howell KE 《Traffic (Copenhagen, Denmark)》2000,1(12):963-975
The known functions of the Golgi complex include the sorting, packaging, post-translational modification, and transport of secretory proteins, membrane proteins, and lipids. Other functions still remain elusive to cell biologists. With the goal of identifying novel Golgi proteins, a proteomics project was undertaken to map the major proteins of the organelle using two-dimensional gels, to identify the unknowns using tandem mass spectrometry, and to screen for Golgi residents using GFP-fusion constructs. Multiple unknowns were identified, and the initial characterization of one of these proteins is reported here. GMx33α is a member of a conserved family of cytosolic Golgi-associated proteins with no known homology to any known functional domain or protein. Biochemical analyses show that GMx33α differentially partitions into all phases of multiple detergent extractions, and two-dimensional immunoblots reveal that there are multiple differentially modified forms of GMx33α associated with the Golgi, several of which are phosphorylated. Evidence suggests that these post-translational modifications regulate its association with the Golgi. GMx33α was not found on Golgi budded vesicles, and immuno-electron microscopy co-localizes GMx33α to the trans -face on the same three cisternae as TGN38 in normal rat kidney cells. This work represents the preliminary characterization of a novel family of trans -Golgi-associated proteins. 相似文献
95.
96.
97.
Genotoxicity of diacetoxyscirpenol (DAS) was studied on laboratory mice after intraperitoneal injection with single and repeated
doses. DAS was administrated at three different dose levels (0.5, 0.75, and 1.0 mg/kg body weight). The study was conducted
on both somatic and germ cells additional to the sperm morphology analysis. DAS treatment resulted in a significant reduction
(P<0.01) in mitotic activity at all levels of doses tested, confirming that DAS is a potent protein and DNA synthesis inhibitor.
At somatic cells (bone marrow) both structural and numerical chromosome abnormalities were observed. Single dose treatment
showed significant abnormalities only with high dose treatment. In contrast, at repeated dose similar abnormalities were also
observed with some significance but no systematic relation between the administrated dose and abnormalities ratio could be
settled. In germ cells (testicles), structural and numerical abnormalities were also observed. In general, the frequencies
of scored abnormalities at germ cells were lower than that the somatic cells. Sperm count test revealed a decrease in the
number of released sperm after toxin treatment. Abnormalities of sperm shape (head and tail) were observed, confirming the
positive correlation between cytogenetic damage and sperm abnormality.
The results also proved that DAS is a very toxic mycotoxin, in addition to inducing chromosomal abnormalities, it causes a
severe inhibition of DNA synthesis which subsequently affects the cell cycle and cell division. A good system for good harvesting
practice and good food technology can lower the risk for the consumers. 相似文献
98.
99.
Increase in striatal acetylcholine levels in vivo by piribedil a new dopamine receptor stimulant 总被引:2,自引:0,他引:2
Piribedil, (1–2″-pyrimidyl)-4-piperonyl piperazine), an agent proposed for the treatment of Parkinson's disease, was found to increase acetylcholine levels in the rat striatum and diencephalon but not in the mesencephalon, cerebellum or hemispheres. The effect was most marked in the striatum (greater than 100%) and long-lasting (at least 8 hours after a single administration of 60 mg/kg i.p.). Striatal choline levels were also increased by piribedil but did not parallel at all times and doses the effect on acetylcholine. Furthermore, choline levels were increased in all brain regions except the hemispheres. Striatal choline acetyltransferase and acetylcholinesterase were not affected by or treatment with even high doses of piribedil. α-Methyl-p-tyrosine was ineffective in blocking piribedil while pimozide, a blocker of dopamine receptors, completely antagonized the action of piribedil on striatal acetylcholine. It is concluded that piribedil produced the increase in striatal acetylcholine by directly stimulating dopamine receptors. 相似文献
100.