Department of Anesthesiology

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CDK5 serves as a major control point in neurotransmitter release.

TitleCDK5 serves as a major control point in neurotransmitter release.
Publication TypeJournal Article
Year of Publication2010
AuthorsKim SHyun, Ryan TA
JournalNeuron
Volume67
Issue5
Pagination797-809
Date Published2010 Sep 9
ISSN1097-4199
Keywords6-Cyano-7-nitroquinoxaline-2,3-dione, Animals, Animals, Newborn, Cyclin-Dependent Kinase 5, Electric Stimulation, Excitatory Amino Acid Antagonists, Gene Expression Regulation, Green Fluorescent Proteins, Hippocampus, Munc18 Proteins, Neurons, Neurotransmitter Agents, Protein Kinase Inhibitors, Purines, Rats, Rats, Sprague-Dawley, RNA, Small Interfering, Sodium Channel Blockers, Synapses, Tetrodotoxin, Transfection, Valine, Vesicle-Associated Membrane Protein 2
Abstract

CDK5 is an important kinase in nervous system function, controlling neural development and postsynaptic signal integration. Here we show that CDK5 plays a major role in controlling neurotransmitter release. Inhibition of CDK5 activity, by either acute or genetic means, leads to profound potentiation of presynaptic function, including unmasking of previously "silent" synapses. Removal of CDK5 activity additionally unlocks access to the resting synaptic vesicle pool, which normally remains recalcitrant to exocytosis and recycling even following prolonged action potential stimuli. Presynaptic CDK5 levels are additionally severely depleted by chronic neuronal silencing, a treatment that is functionally similar to CDK5 knockdown with regard to presynaptic potentiation. Thus CDK5 appears to be an integral element in presynaptic homeostatic scaling, and the resting vesicle pool appears to provide a potent functional presynaptic homeostatic control parameter. These studies thus pinpoint CDK5 as a major control point for modulation of neurotransmitter release in mammalian neurons.

DOI10.1016/j.neuron.2010.08.003
Alternate JournalNeuron
PubMed ID20826311
PubMed Central IDPMC2939042
Grant ListMH085783 / MH / NIMH NIH HHS / United States
NS036942 / NS / NINDS NIH HHS / United States
R01 MH085783-01A1 / MH / NIMH NIH HHS / United States
R01 MH085783-02 / MH / NIMH NIH HHS / United States
R01 NS036942-13 / NS / NINDS NIH HHS / United States
R01 NS036942-15 / NS / NINDS NIH HHS / United States