کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1940126 1050774 2006 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Biochemical investigation of Tau protein phosphorylation status and its solubility properties in Drosophila
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Biochemical investigation of Tau protein phosphorylation status and its solubility properties in Drosophila
چکیده انگلیسی

Tau hyperphosphorylation and insoluble aggregate formation are two cellular features of tauopathies. However, the contribution of Tau protein hyperphosphorylation and its aggregation to Tau pathology still remain controversial. Overexpression of human tau transgenes in the Drosophila eye is toxic and causes neuronal degeneration. We showed that human Tau protein was phosphorylated by endogenous protein kinases in flies, and overexpression of either GSK3β or Cdk5 enhanced tau-induced toxicity. Using a dominant-negative approach, we showed that kinase activity is important for the enhancement of tau-induced toxicity. Interestingly, such enhancement was accompanied with hyperphosphorylation and alteration of protein solubility properties of Tau. This situation was reminiscent of that observed in pre-tangle neurons in tauopathies patients. We also observed age-dependent Tau aggregate formation in aged transgenic flies. In summary, tau-induced toxicity is enhanced when the human Tau protein undergoes hyperphosphorylation, and we further demonstrated that aging contributes to Tau aggregate formation. Our data also underscore the utilization of transgenic Drosophila Tau models for the studies of pre-tangle events in tauopathies.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 346, Issue 1, 21 July 2006, Pages 150–159
نویسندگان
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