排序方式: 共有68条查询结果,搜索用时 401 毫秒
1.
γ-secretase, which assembles as a tetrameric complex, is an aspartyl protease that proteolytically cleaves substrate proteins within their membrane-spanning domain; a process also known as regulated intramembrane proteolysis (RIP). RIP regulates signaling pathways by abrogating or releasing signaling molecules. Since the discovery, already > 15 years ago, of its catalytic component, presenilin, and even much earlier with the identification of amyloid precursor protein as its first substrate, γ-secretase has been commonly associated with Alzheimer's disease. However, starting with Notch and thereafter a continuously increasing number of novel substrates, γ-secretase is becoming linked to an equally broader range of biological processes. This review presents an updated overview of the current knowledge on the diverse molecular mechanisms and signaling pathways controlled by γ-secretase, with a focus on organ development, homeostasis and dysfunction. This article is part of a Special Issue entitled: Intramembrane Proteases. 相似文献
2.
3.
4.
Rosanne Wouters Christine Michiels Ragna Sannerud Bertrand Kleizen Katleen Dillen Wendy Vermeire Abril Escamilla Ayala David Demedts Randy Schekman Wim Annaert 《The Journal of cell biology》2021,220(9)
γ-Secretase affects many physiological processes through targeting >100 substrates; malfunctioning links γ-secretase to cancer and Alzheimer’s disease. The spatiotemporal regulation of its stoichiometric assembly remains unresolved. Fractionation, biochemical assays, and imaging support prior formation of stable dimers in the ER, which, after ER exit, assemble into full complexes. In vitro ER budding shows that none of the subunits is required for the exit of others. However, knockout of any subunit leads to the accumulation of incomplete subcomplexes in COPII vesicles. Mutating a DPE motif in presenilin 1 (PSEN1) abrogates ER exit of PSEN1 and PEN-2 but not nicastrin. We explain this by the preferential sorting of PSEN1 and nicastrin through Sec24A and Sec24C/D, respectively, arguing against full assembly before ER exit. Thus, dimeric subcomplexes aided by Sec24 paralog selectivity support a stepwise assembly of γ-secretase, controlling final levels in post-Golgi compartments. 相似文献
5.
Foulquier F Amyere M Jaeken J Zeevaert R Schollen E Race V Bammens R Morelle W Rosnoblet C Legrand D Demaegd D Buist N Cheillan D Guffon N Morsomme P Annaert W Freeze HH Van Schaftingen E Vikkula M Matthijs G 《American journal of human genetics》2012,91(1):15-26
Protein glycosylation is a complex process that depends not only on the activities of several enzymes and transporters but also on a subtle balance between vesicular Golgi trafficking, compartmental pH, and ion homeostasis. Through a combination of autozygosity mapping and expression analysis in two siblings with an abnormal serum-transferrin isoelectric focusing test (type 2) and a peculiar skeletal phenotype with epiphyseal, metaphyseal, and diaphyseal dysplasia, we identified TMEM165 (also named TPARL) as a gene involved in congenital disorders of glycosylation (CDG). The affected individuals are homozygous for a deep intronic splice mutation in TMEM165. In our cohort of unsolved CDG-II cases, we found another individual with the same mutation and two unrelated individuals with missense mutations in TMEM165. TMEM165 encodes a putative transmembrane 324 amino acid protein whose cellular functions are unknown. Using a siRNA strategy, we showed that TMEM165 deficiency causes Golgi glycosylation defects in HEK cells. 相似文献
6.
Interaction with telencephalin and the amyloid precursor protein predicts a ring structure for presenilins. 总被引:15,自引:0,他引:15
W G Annaert C Esselens V Baert C Boeve G Snellings P Cupers K Craessaerts B De Strooper 《Neuron》2001,32(4):579-589
The carboxyl terminus of presenilin 1 and 2 (PS1 and PS2) binds to the neuron-specific cell adhesion molecule telencephalin (TLN) in the brain. PS1 deficiency results in the abnormal accumulation of TLN in a yet unidentified intracellular compartment. The first transmembrane domain and carboxyl terminus of PS1 form a binding pocket with the transmembrane domain of TLN. Remarkably, APP binds to the same regions via part of its transmembrane domain encompassing the critical residues mutated in familial Alzheimer's disease. Our data surprisingly indicate a spatial dissociation between the binding site and the proposed catalytic site near the critical aspartates in PSs. They provide important experimental evidence to support a ring structure model for PS. 相似文献
7.
Dirk Slembrouck Peter Partoens Wim Annaert Werner P. De Potter 《Methods (San Diego, Calif.)》1999,18(4):465
The study of secretory vesicle dynamics is a continuing challenge. Classically it was studied using biochemical techniques, such as subcellular fractionation and immunoprecipitation, combined with time-consuming electron microscopy studies. The recent development of confocal microscopy, giving in-focus optical section images throughout the thickness of a fluorescently labeled sample, allows scientists to study the key events in the secretory cycle at the level of light microscopy. This study demonstrates the use of specific antibodies against marker proteins of two different secretory vesicles (synaptic vesicles and large dense-cored vesicles) to follow their exo–endocytosis dynamics in peripheral adrenergic neurons. Only in recent years has insight grown regarding the presence of both exocytosis pathways in the same neuron. Confocal microscopy is a suitable technique to study aspects of exocytosis, endocytosis, and intracellular sorting and as such improves our knowledge on the interaction between both secretory pathways. 相似文献
8.
Patrick M Bossuyt Johannes B Reitsma David E Bruns Constantine A Gatsonis Paul P Glasziou Les M Irwig Jeroen G Lijmer David Moher Drummond Rennie Henrica C W de Vet 《BMJ (Clinical research ed.)》2003,326(7379):41-44
ObjectiveTo improve the accuracy and completeness of reporting of studies of diagnostic accuracy, to allow readers to assess the potential for bias in a study, and to evaluate a study''s generalisability.MethodsThe Standards for Reporting of Diagnostic Accuracy (STARD) steering committee searched the literature to identify publications on the appropriate conduct and reporting of diagnostic studies and extracted potential items into an extensive list. Researchers, editors, and members of professional organisations shortened this list during a two day consensus meeting, with the goal of developing a checklist and a generic flow diagram for studies of diagnostic accuracy.ResultsThe search for published guidelines about diagnostic research yielded 33 previously published checklists, from which we extracted a list of 75 potential items. At the consensus meeting, participants shortened the list to a 25 item checklist, by using evidence, whenever available. A prototype of a flow diagram provides information about the method of patient recruitment, the order of test execution, and the numbers of patients undergoing the test under evaluation and the reference standard, or both.ConclusionsEvaluation of research depends on complete and accurate reporting. If medical journals adopt the STARD checklist and flow diagram, the quality of reporting of studies of diagnostic accuracy should improve to the advantage of clinicians, researchers, reviewers, journals, and the public.The Standards for Reporting of Diagnostic Accuracy (STARD) steering group aims to improve the accuracy and completeness of reporting of studies of diagnostic accuracy. The group describes and explains the development of a checklist and flow diagram for authors of reports 相似文献
9.
Chromogranin A (CGA) has been localized to the large dense cored vesicles (LDV) of sympathetic neurons. SDS-PAGE and immunoblotting of soluble LDV proteins from ox and dog adrenergic neuronal cell bodies, axons and nerve terminals, revealed an increasing number of CGA-immunoreactive forms, consistent with proteolytic processing during axonal transport. Splenic nerve electrical stimulation (10 Hz, 2 min) revealed that, apart from CGA, these CGA-processing products are released from the sheep spleen. The secretion of CGA-derived fragments from sympathetic neurons might suggest a role in the regulation of synaptic transmission. 相似文献
10.
Psychometric evaluation of the Orofacial Pain Scale for Non‐Verbal Individuals as a screening tool for orofacial pain in people with dementia
下载免费PDF全文
![点击此处可从《Gerodontology》网站下载免费的PDF全文](/ch/ext_images/free.gif)
Suzanne Delwel Andrea B. Maier Cees M. P. M. Hertogh Henrica C. W. de Vet Frank Lobbezoo Erik J. A. Scherder 《Gerodontology》2018,35(3):200-213