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PMID: 18498738 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Critical role of CDK5 and Polo-like kinase 2 in homeostatic synaptic plasticity during elevated activity.

Neuron ·Vol. 58 ·No. 4 ·2008-05-22 ·Pages 571-83

Seeburg DP, Feliu-Mojer M, Gaiottino J, Pak DT, Sheng M

Abstract

Homeostatic plasticity keeps neuronal spiking output within an optimal range in the face of chronically altered levels of network activity. Little is known about the underlying molecular mechanisms, particularly in response to elevated activity. We report that, in hippocampal neurons experiencing heightened activity, the activity-inducible protein kinase Polo-like kinase 2 (Plk2, also known as SNK) was required for synaptic scaling-a principal mechanism underlying homeostatic plasticity. Synaptic scaling also required CDK5, which acted as a "priming" kinase for the phospho-dependent binding of Plk2 to its substrate SPAR, a postsynaptic RapGAP and scaffolding molecule that is degraded following phosphorylation by Plk2. RNAi knockdown of SPAR weakened synapses, and overexpression of a SPAR mutant resistant to Plk2-dependent degradation prevented synaptic scaling. Thus, priming phosphorylation of the Plk2 binding site in SPAR by CDK5, followed by Plk2 recruitment and SPAR phosphorylation-degradation, constitutes a molecular pathway for neuronal homeostatic plasticity during chronically elevated activity.

MeSH Terms
Animals Cells, Cultured Cyclin-Dependent Kinase 5/physiology Embryo, Mammalian Excitatory Postsynaptic Potentials Green Fluorescent Proteins/genetics,metabolism Hippocampus/cytology Humans Immunoprecipitation Membrane Potentials/physiology,radiation effects Nerve Tissue Proteins/metabolism Neuronal Plasticity/physiology Neurons/cytology,physiology Patch-Clamp Techniques Phosphorylation Protein Kinases/physiology RNA Interference/physiology Rats Rats, Sprague-Dawley Serine/metabolism Synapses/physiology Transfection/methods
Chemicals
Nerve Tissue Proteins Green Fluorescent Proteins Serine Protein Kinases Cyclin-Dependent Kinase 5 Cdk5 protein, rat
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Seeburg Daniel P
The Picower Institute for Learning and Memory, RIKEN-MIT Neuroscience Research Center, Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Feliu-Mojer Monica
Gaiottino Johanna
Pak Daniel T S
Sheng Morgan
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Article Info
Journal
Neuron
Abbr.
Neuron
ISSN
1097-4199
DOI
10.1016/j.neuron.2008.03.021
Published
2008-05-22
Pages
571-83
Language
English
Region
United States
NLM ID
8809320
PMCID
PMC2488274
Subset
IM
Grants
Howard Hughes Medical Institute · United States
NINDS NIH HHS · R01 NS048085 · United States
NINDS NIH HHS · R01 NS048085-04 · United States
External Links
PubMed source DOI: 10.1016/j.neuron.2008.03.021 PMC Full Text View journal details
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