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CDK5 Serves as a Major Control Point in Neurotransmitter Release
Open accessAbstract
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 KD 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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Cites
HOMEOSTATIC CONTROL OF NEURAL ACTIVITY: From Phenomenology to Molecular Design
Davis, G. W. (2006) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.28.061604.135751 · Cited by 543
Balaji, J., & Ryan, T. A. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0707574105 · Cited by 279
Self-citation
Cited by
Neuropeptide Transmission in Brain Circuits
van den Pol, A. N. (2012) · Neuron · doi:10.1016/j.neuron.2012.09.014 · Cited by 810
Activity-driven local ATP synthesis is required for synaptic function
Rangaraju, V., Calloway, N., & Ryan, T. A. (2014) · Cell · doi:10.1016/j.cell.2013.12.042 · Cited by 836
Self-citationA trans-synaptic nanocolumn aligns neurotransmitter release to receptors
Tang, A.-H., Chen, H., Li, T. P., Metzbower, S. R., MacGillavry, H. D., & Blanpied, T. A. (2016) · Nature · doi:10.1038/nature19058 · Cited by 677
α2δ expression sets presynaptic calcium channel abundance and release probability
Hoppa, M. B., Lana, B., Margas, W., Dolphin, A. C., & Ryan, T. A. (2012) · Nature · doi:10.1038/nature11033 · Cited by 358
Self-citationSynaptic vesicle recycling: steps and principles
Rizzoli, S. O. (2014) · The EMBO Journal · doi:10.1002/embj.201386357 · Cited by 317
Metadata
- Authors
- Kim, S. H., & Ryan, T. A.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2010-09
- Volume
- 67
- Issue
- 5
- Pages
- 797-809
- ISSN
- 0896-6273 (ISSN-L)
- OpenAlex
- W2082443574
- Cited by
- 275
- References
- 2
- FWCI
- 8.90
- Type
- journal article
- Language
- en
- Open access
- bronze
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
