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Bi‐directional regulation of postsynaptic cortactin distribution by BDNF and NMDA receptor activity
Author(s) -
Iki Junko,
Inoue Akihiro,
Bito Haruhiko,
Okabe Shigeo
Publication year - 2005
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2005.04510.x
Subject(s) - cortactin , postsynaptic potential , postsynaptic density , microbiology and biotechnology , nmda receptor , excitatory postsynaptic potential , proto oncogene tyrosine protein kinase src , chemistry , biology , inhibitory postsynaptic potential , neuroscience , phosphorylation , receptor , cytoskeleton , biochemistry , cell
Cortactin is an F‐actin‐associated protein which interacts with the postsynaptic scaffolding protein Shank at the SH3 domain and is localized within the dendritic spine in the mouse neuron. Green fluorescent protein (GFP)‐based time‐lapse imaging revealed cortactin redistribution from dendritic cytoplasm to postsynaptic sites by application of brain‐derived neurotrophic factor (BDNF). This response was mediated by mitogen‐activated protein (MAP) kinase activation and was dependent on the C‐terminal SH3 domain. In contrast, activation of N ‐methyl‐ d ‐aspartate (NMDA) receptors induced loss of cortactin from postsynaptic sites. This NMDA‐dependent redistribution was blocked by an Src family kinase inhibitor. Conversely, increasing Src family kinase activity induced cortactin phosphorylation and loss of cortactin from the postsynaptic sites. Finally, blocking of endogenous BDNF reduced the amount of cortactin at the postsynaptic sites and an NMDA receptor antagonist prevented this reduction. These results indicate the importance of counterbalance between BDNF and NMDA receptor‐mediated signalling in the reorganization of the postsynaptic actin cytoskeleton during neuronal development.