Assembly of γ-secretase occurs through stable dimers after exit from the endoplasmic reticulum
| العنوان: | Assembly of γ-secretase occurs through stable dimers after exit from the endoplasmic reticulum |
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| المؤلفون: | Wim Annaert, Katleen Dillen, Randy Schekman, Ragna Sannerud, Bertrand Kleizen, Rosanne Wouters, David Demedts, Christine Michiels, Abril Escamilla Ayala, Wendy Vermeire |
| المصدر: | Journal of Cell Biology, 220(9), 1. Rockefeller University Press |
| بيانات النشر: | Rockefeller University Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Models, Molecular, Endopeptidases/chemistry, Protein Conformation, Vesicular Transport Proteins, Wistar, Golgi Apparatus, Endoplasmic Reticulum, Mice, Neurons/cytology, 0302 clinical medicine, COP-Coated Vesicles/chemistry, Models, COMPLEX COMPONENT, PSEN1, Protein Isoforms, Endoplasmic Reticulum/metabolism, COPII, Cerebral Cortex, Neurons, Golgi Apparatus/metabolism, 0303 health sciences, Budding, Tumor, biology, MEMBRANE-PROTEINS, Vesicle, ER RETENTION, Cell biology, AMYLOID PRECURSOR PROTEIN, ALZHEIMERS-DISEASE, COP-Coated Vesicles, Life Sciences & Biomedicine, Cerebral Cortex/cytology, Protein Binding, Signal Transduction, STRUCTURAL BASIS, COPII VESICLES, PRESENILIN-1, Protein subunit, Primary Cell Culture, Protein Isoforms/chemistry, Nicastrin, Amyloid Precursor Protein Secretases/chemistry, Presenilin, Cell Line, Vesicular Transport Proteins/genetics, 03 medical and health sciences, QUALITY-CONTROL, Cell Line, Tumor, Presenilin-1/chemistry, Endopeptidases, Presenilin-1, Animals, Humans, Rats, Wistar, 030304 developmental biology, Science & Technology, Endoplasmic reticulum, Membrane Proteins, Molecular, Membrane Proteins/chemistry, Biological Transport, Cell Biology, Fibroblasts, Rats, Fibroblasts/cytology, Gene Expression Regulation, biology.protein, INTERMEDIATE COMPARTMENT, Amyloid Precursor Protein Secretases, Protein Multimerization, 030217 neurology & neurosurgery |
| الوصف: | 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. ispartof: JOURNAL OF CELL BIOLOGY vol:220 issue:9 ispartof: location:United States status: published |
| وصف الملف: | application/pdf; Print-Electronic |
| تدمد: | 1540-8140 0021-9525 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::09d9039d96590f096bfacb0662aeabdbTest https://doi.org/10.1083/jcb.201911104Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....09d9039d96590f096bfacb0662aeabdb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15408140 00219525 |
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