Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage
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Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage. / Matsumoto-Miyai, Kazumasa; Sokolowska, Ewa; Zurlinden, Andreas; Gee, Christine E; Lüscher, Daniel; Hettwer, Stefan; Wölfel, Jens; Ladner, Ana Paula; Ster, Jeanne; Gerber, Urs; Rülicke, Thomas; Kunz, Beat; Sonderegger, Peter.
in: CELL, Jahrgang 136, Nr. 6, 20.03.2009, S. 1161-71.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Coincident pre- and postsynaptic activation induces dendritic filopodia via neurotrypsin-dependent agrin cleavage
AU - Matsumoto-Miyai, Kazumasa
AU - Sokolowska, Ewa
AU - Zurlinden, Andreas
AU - Gee, Christine E
AU - Lüscher, Daniel
AU - Hettwer, Stefan
AU - Wölfel, Jens
AU - Ladner, Ana Paula
AU - Ster, Jeanne
AU - Gerber, Urs
AU - Rülicke, Thomas
AU - Kunz, Beat
AU - Sonderegger, Peter
PY - 2009/3/20
Y1 - 2009/3/20
N2 - The 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.
AB - The 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.
KW - Agrin
KW - Animals
KW - Cell Line
KW - Dendrites
KW - Exocytosis
KW - Hippocampus
KW - Humans
KW - In Vitro Techniques
KW - Mice
KW - Mice, Transgenic
KW - Mutagenesis
KW - Presynaptic Terminals
KW - Pseudopodia
KW - Serine Endopeptidases
U2 - 10.1016/j.cell.2009.02.034
DO - 10.1016/j.cell.2009.02.034
M3 - SCORING: Journal article
C2 - 19303856
VL - 136
SP - 1161
EP - 1171
JO - CELL
JF - CELL
SN - 0092-8674
IS - 6
ER -