کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8839746 | 1613752 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
FUS causes synaptic hyperexcitability in Drosophila dendritic arborization neurons
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کلمات کلیدی
CSPdendritic arborization - arborization دندریتیکFUs - FUSALS - بیماری اسکلروز جانبی آمیوتروفیکNuclear transport - حمل و نقل هسته ایCabeza - سرSynaptotagmin - سیناپتوتاگمینCaz - موردDrosophila - مگس سرکهNeuron - نورونSynapse - همایه یا سیناپسCysteine string protein - پروتئین رشته سیستینFlag - پرچمSYT - چشم
موضوعات مرتبط
علوم زیستی و بیوفناوری
علم عصب شناسی
علوم اعصاب (عمومی)
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چکیده انگلیسی
Mutations in the nuclear localization signal of the RNA binding protein FUS cause both Frontotemporal Dementia (FTD) and Amyotrophic Lateral Sclerosis (ALS). These mutations result in a loss of FUS from the nucleus and the formation of FUS-containing cytoplasmic aggregates in patients. To better understand the role of cytoplasmic FUS mislocalization in the pathogenesis of ALS, we identified a population of cholinergic neurons in Drosophila that recapitulate these pathologic hallmarks. Expression of mutant FUS or the Drosophila homolog, Cabeza (Caz), in class IV dendritic arborization neurons results in cytoplasmic mislocalization and axonal transport to presynaptic terminals. Interestingly, overexpression of FUS or Caz causes the progressive loss of neuronal projections, reduction of synaptic mitochondria, and the appearance of large calcium transients within the synapse. Additionally, we find that overexpression of mutant but not wild type FUS results in a reduction in presynaptic Synaptotagmin, an integral component of the neurotransmitter release machinery, and mutant Caz specifically disrupts axonal transport and induces hyperexcitability. These results suggest that FUS/Caz overexpression disrupts neuronal function through multiple mechanisms, and that ALS-causing mutations impair the transport of synaptic vesicle proteins and induce hyperexcitability.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Brain Research - Volume 1693, Part A, 15 August 2018, Pages 55-66
Journal: Brain Research - Volume 1693, Part A, 15 August 2018, Pages 55-66
نویسندگان
James B. Machamer, Brian M. Woolums, Gregory G. Fuller, Thomas E. Lloyd,