CDK5 Serves as a Major Control Point in Neurotransmitter Release

Sung Hyun Kim; Timothy A. Ryan

doi:10.1016/j.neuron.2010.08.003

CDK5 Serves as a Major Control Point in Neurotransmitter Release

Sung Hyun Kim
, Timothy A. Ryan

Research output: Contribution to journal › Article › peer-review

236 Citations (Scopus)

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.

Original language	English
Pages (from-to)	797-809
Number of pages	13
Journal	Neuron
Volume	67
Issue number	5
DOIs	https://doi.org/10.1016/j.neuron.2010.08.003
Publication status	Published - Sept 2010

Bibliographical note

Funding Information:
The authors would like to thank Jeremy Dittman and members of the Ryan lab for valuable discussions. We thank Ricky Kwan for excellent technical assistance. vG-pH was a gift from Rob Edwards and Susan Voglamaier (UCSF). This work was supported in part by NIH grants to T.A.R. (NS036942 and MH085783) and a sponsored research agreement with Galenea Corp (Cambridge, MA). T.A.R. is a consultant with Galena Corp, which provided some financial support for the work reported here.

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title = "CDK5 Serves as a Major Control Point in Neurotransmitter Release",

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.",

author = "Kim, \{Sung Hyun\} and Ryan, \{Timothy A.\}",

note = "Funding Information: The authors would like to thank Jeremy Dittman and members of the Ryan lab for valuable discussions. We thank Ricky Kwan for excellent technical assistance. vG-pH was a gift from Rob Edwards and Susan Voglamaier (UCSF). This work was supported in part by NIH grants to T.A.R. (NS036942 and MH085783) and a sponsored research agreement with Galenea Corp (Cambridge, MA). T.A.R. is a consultant with Galena Corp, which provided some financial support for the work reported here. ",

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AU - Ryan, Timothy A.

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PY - 2010/9

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N2 - 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.

AB - 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.

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CDK5 Serves as a Major Control Point in Neurotransmitter Release

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