کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1950896 1055720 2011 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Calmodulin regulates the non-amyloidogenic metabolism of amyloid precursor protein in platelets
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Calmodulin regulates the non-amyloidogenic metabolism of amyloid precursor protein in platelets
چکیده انگلیسی

A balance between the proteolytic processing of amyloid precursor protein APP through the amyloidogenic and the non-amyloidogenic pathways controls the production and release of amyloid β-protein, whose accumulation in the brain is associated to the onset of Alzheimer Disease. APP is also expressed on circulating platelets. The regulation of APP processing in these cells is poorly understood. In this work we show that platelets store considerable amounts of APP fragments, including sAPPα, that can be released upon stimulation of platelets. Moreover, platelet stimulation also promotes the proteolysis of intact APP expressed on the cell surface. This process is supported by an ADAM metalloproteinase, and causes the release of sAPPα. Processing of intact platelet APP is promoted also by treatment with calmodulin antagonist W7. W7-induced APP proteolysis occurs through the non-amyloidogenic pathway, is mediated by a metalloproteinase, and causes the release of sAPPα. Co-immunoprecipitation and pull-down experiments revealed a physical association between calmodulin and APP. These results document a novel role of calmodulin in the regulation of non-amyloidogenic processing of APP.

Research highlights
► Agonist platelets induce proteolysis of APP through the non-amyloidogenic pathway.
► Calmodulin antagonist promotes APP proteolysis in resting platelets.
► Calmodulin is a binding partner for APP in platelets.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochimica et Biophysica Acta (BBA) - Molecular Cell Research - Volume 1813, Issue 3, March 2011, Pages 500–506
نویسندگان
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