Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Activity-dependent modifications in synapse structure play a key role in synaptic development and plasticity, but the signaling mechanisms involved are poorly understood. We demonstrate that glutamatergic Drosophila neuromuscular junctions undergo rapid changes in synaptic structure and function in response to patterned stimulation. These changes, which depend on transcription and translation, include formation of motile presynaptic filopodia, elaboration of undifferentiated varicosities, and potentiation of spontaneous release frequency. Experiments indicate that a bidirectional Wnt/Wg signaling pathway underlies these changes. Evoked activity induces Wnt1/Wg release from synaptic boutons, which stimulates both a postsynaptic DFz2 nuclear import pathway as well as a presynaptic pathway involving GSK-3beta/Shaggy. Our findings suggest that bidirectional Wg signaling operates downstream of synaptic activity to induce modifications in synaptic structure and function. We propose that activation of the postsynaptic Wg pathway is required for the assembly of the postsynaptic apparatus, while activation of the presynaptic Wg pathway regulates cytoskeletal dynamics.
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PMID:Rapid activity-dependent modifications in synaptic structure and function require bidirectional Wnt signaling. 1834 91

Hippocampal control of memory formation is regulated by dopaminergic signaling. Whereas the role of dopamine D1 receptors is well documented in such regulations, functions of dopamine D2 receptors (DRD2) are not fully understood. Using fluorescence in situ hybridization we demonstrate that Drd2 expression in the hippocampus of wild-type mice is limited to glutamatergic hilar mossy cells. Using whole cell electrophysiological recordings in hippocampal slice preparations, we provide evidence that unlike in basal ganglia, activation of DRD2 by the selective agonist, quinpirole, induces a long-lasting increase in excitability of hilar mossy cells, which can be blocked by the DRD2 antagonist raclopride. Such activity is mediated by the Akt/GSK pathway, as application of specific inhibitors such as A1070722 or SB216763 prevented quinpirole activity. Long-term effects of acute DRD2 activation in vitro suggest that volume transmission of dopamine may modulate mossy cell activities in vivo. This is supported by the presence of dense tyrosine hydroxylase positive varicosities in the hilus, which are rarely seen in the vicinity of mossy cell dendrites. From these data we discuss how dopamine could control mossy cell activity and thus dentate gyrus functions.
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PMID:Dopamine D2 receptor controls hilar mossy cells excitability. 2475 32