دورية أكاديمية
Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membrane.
| العنوان: | Huntingtin is required for ER-to-Golgi transport and for secretory vesicle fusion at the plasma membrane. |
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| المؤلفون: | Brandstaetter, Hemma, Kruppa, Antonina J, Buss, Folma |
| بيانات النشر: | //dx.doi.org/10.1242/dmm.017368 Dis Model Mech The Company of Biologists |
| سنة النشر: | 2014 |
| المجموعة: | Apollo - University of Cambridge Repository |
| مصطلحات موضوعية: | ER, Exocytosis, Golgi, Huntingtin, Vesicle fusion, Animals, Cell Membrane, Disease Models, Animal, Endoplasmic Reticulum, Fibroblasts, Golgi Apparatus, Green Fluorescent Proteins, HeLa Cells, Homozygote, Humans, Huntingtin Protein, Huntington Disease, Mice, Microscopy, Fluorescence, Nerve Tissue Proteins, Nuclear Proteins, Protein Binding, Protein Transport, RNA, Small Interfering, Secretory Vesicles, trans-Golgi Network |
| الوصف: | Huntingtin is a large membrane-associated scaffolding protein that associates with endocytic and exocytic vesicles and modulates their trafficking along cytoskeletal tracks. Although the progression of Huntington's disease is linked to toxic accumulation of mutant huntingtin protein, loss of wild-type huntingtin function might also contribute to neuronal cell death, but its precise function is not well understood. Therefore, we investigated the molecular role of huntingtin in exocytosis and observed that huntingtin knockdown in HeLa cells causes a delay in endoplasmic reticulum (ER)-to-Golgi transport and a reduction in the number of cargo vesicles leaving the trans-Golgi network. In addition, we found that huntingtin is required for secretory vesicle fusion at the plasma membrane. Similar defects in the early exocytic pathway were observed in primary fibroblasts from homozygous Htt(140Q/140Q) knock-in mice, which have the expansion inserted into the mouse huntingtin gene so lack wild-type huntingtin expression. Interestingly, heterozygous fibroblasts from a Huntington's disease patient with a 180Q expansion displayed no obvious defects in the early secretory pathway. Thus, our results highlight the requirement for wild-type huntingtin at distinct steps along the secretory pathway. ; This work was supported by the Cure Huntingtin’s Disease Initiative (CHDI) (H.B. and A.J.K.), the Wellcome Trust (grant number 086743 to F.B.) and the Medical Research Council (grant number MR/K000888/1 to F.B). The CIMR is in receipt of a strategic award from the Wellcome Trust (grant number 100140). ; This is the accepted manuscript. It first appeared at http://dmm.biologists.org/content/early/2014/10/30/dmm.017368Test. |
| نوع الوثيقة: | article in journal/newspaper |
| وصف الملف: | application/pdf |
| اللغة: | English |
| العلاقة: | https://www.repository.cam.ac.uk/handle/1810/246722Test |
| الإتاحة: | https://www.repository.cam.ac.uk/handle/1810/246722Test |
| حقوق: | Attribution 2.0 UK: England & Wales ; http://creativecommons.org/licenses/by/2.0/ukTest/ |
| رقم الانضمام: | edsbas.19F986FB |
| قاعدة البيانات: | BASE |
| الوصف غير متاح. |