کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8478502 | 1551135 | 2016 | 49 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Control of spine maturation and pruning through proBDNF synthesized and released in dendrites
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کلمات کلیدی
TrkBMHCINLSFMRPp75NTRTTXBDNF - BDNF یا فاکتور نورونزایی مشتقشده از مغز tetrodotoxin - تترو دوتوکسین DIV - دیوday in vitro - روز in vitroLocal protein synthesis - سنتز پروتئین محلیnuclear localization signal - سیگنال محلی سازی هسته ایBrain-derived neurotrophic factor - فاکتور نوروتروفی مشتق شده از مغزUTR یا untranslated regions - منطقه ترجمه نشدهuntranslated region - منطقه غیر ترجمهMyr - میرfragile X mental retardation protein - پروتئین عقب ماندگی ذهنی X شکننده استMajor Histocompatibility Class I - کلاس اصلی بافت سازگاری
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
بیولوژی سلول
پیش نمایش صفحه اول مقاله
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چکیده انگلیسی
Excess synapses formed during early postnatal development are pruned over an extended period, while the remaining synapses mature. Synapse pruning is critical for activity-dependent refinement of neuronal connections and its dysregulation has been found in neurodevelopmental disorders such as autism spectrum disorders; however, the mechanism underlying synapse pruning remains largely unknown. As dendritic spines are the postsynaptic sites for the vast majority of excitatory synapses, spine maturation and pruning are indicators for maturation and elimination of these synapses. Our previous studies have found that dendritically localized mRNA for brain-derived neurotrophic factor (BDNF) regulates spine maturation and pruning. Here we investigated the mechanism by which dendritic Bdnf mRNA, but not somatically restricted Bdnf mRNA, promotes spine maturation and pruning. We found that neuronal activity stimulates both translation of dendritic Bdnf mRNA and secretion of its translation product mainly as proBDNF. The secreted proBDNF promotes spine maturation and pruning, and its effect on spine pruning is in part mediated by the p75NTR receptor via RhoA activation. Furthermore, some proBDNF is extracellularly converted to mature BDNF and then promotes maturation of stimulated spines by activating Rac1 through the TrkB receptor. In contrast, translation of somatic Bdnf mRNA and the release of its translation product mainly as mature BDNF are independent of action potentials. These results not only reveal a biochemical pathway regulating synapse pruning, but also suggest that BDNF synthesized in the soma and dendrites is released through distinct secretory pathways.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Molecular and Cellular Neuroscience - Volume 71, March 2016, Pages 66-79
Journal: Molecular and Cellular Neuroscience - Volume 71, March 2016, Pages 66-79
نویسندگان
Lauren L. Orefice, Chien-Cheng Shih, Haifei Xu, Emily G. Waterhouse, Baoji Xu,