کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2036882 1072288 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Coincident Pre- and Postsynaptic Activation Induces Dendritic Filopodia via Neurotrypsin-Dependent Agrin Cleavage
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی بیوشیمی، ژنتیک و زیست شناسی مولکولی (عمومی)
پیش نمایش صفحه اول مقاله
Coincident Pre- and Postsynaptic Activation Induces Dendritic Filopodia via Neurotrypsin-Dependent Agrin Cleavage
چکیده انگلیسی

SummaryThe synaptic serine protease neurotrypsin is essential for cognitive function, as its deficiency in humans results in severe mental retardation. Recently, we demonstrated the activity-dependent release of neurotrypsin from presynaptic terminals and proteolytical cleavage of agrin at the synapse. Here we show that the activity-dependent formation of dendritic filopodia is abolished in hippocampal neurons from neurotrypsin-deficient mice. Administration of the neurotrypsin-dependent 22 kDa fragment of agrin rescues the filopodial response. Detailed analyses indicated that presynaptic action potential firing is necessary for the release of neurotrypsin, whereas postsynaptic NMDA receptor activation is necessary for the neurotrypsin-dependent cleavage of agrin. This contingency characterizes the neurotrypsin-agrin system as a coincidence detector of pre- and postsynaptic activation. As the resulting dendritic filopodia are thought to represent precursors of synapses, the neurotrypsin-dependent cleavage of agrin at the synapse may be instrumental for a Hebbian organization and remodeling of synaptic circuits in the CNS.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: - Volume 136, Issue 6, 20 March 2009, Pages 1161–1171
نویسندگان
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