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PMID:12873385

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Citation

Fink, CC, Bayer, KU, Myers, JW, Ferrell, JE Jr, Schulman, H and Meyer, T (2003) Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII. Neuron 39:283-97

Abstract

Neurite extension and branching are important neuronal plasticity mechanisms that can lead to the addition of synaptic contacts in developing neurons and changes in the number of synapses in mature neurons. Here we show that Ca2+/calmodulin-dependent protein kinase II (CaMKII) regulates movement, extension, and branching of filopodia and fine dendrites as well as the number of synapses in hippocampal neurons. Only CaMKIIbeta, which peaks in expression early in development, but not CaMKIIalpha, has this morphogenic activity. A small insert in CaMKIIbeta, which is absent in CaMKIIalpha, confers regulated F-actin localization to the enzyme and enables selective upregulation of dendritic motility. These results show that the two main neuronal CaMKII isoforms have markedly different roles in neuronal plasticity, with CaMKIIalpha regulating synaptic strength and CaMKIIbeta controlling the dendritic morphology and number of synapses.

Links

PubMed

Keywords

Actins/metabolism; Animals; Animals, Newborn; Bacterial Proteins/metabolism; Benzylamines; Binding Sites; Calcium-Calmodulin-Dependent Protein Kinase Type 2; Calcium-Calmodulin-Dependent Protein Kinases/classification; Calcium-Calmodulin-Dependent Protein Kinases/genetics; Calcium-Calmodulin-Dependent Protein Kinases/physiology; Cell Fractionation/methods; Cell Movement; Cells, Cultured; Dose-Response Relationship, Drug; Enzyme Inhibitors/pharmacology; Gene Expression Regulation, Enzymologic; Green Fluorescent Proteins; Immunoblotting; Immunohistochemistry; Isoquinolines/metabolism; Luminescent Proteins/metabolism; Microscopy, Confocal; Mutation; Nerve Tissue Proteins/metabolism; Neurites/drug effects; Neurites/physiology; Protein Isoforms/genetics; Protein Isoforms/physiology; RNA Interference/physiology; Rats; Sulfonamides; Synapses/drug effects; Synapses/physiology; Time Factors; Transfection

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

RAT:KCC2B

involved_in

GO:0010976: positive regulation of neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:KCC2B

involved_in

GO:0061003: positive regulation of dendritic spine morphogenesis

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

RAT:KCC2B

involved_in

GO:0090129: positive regulation of synapse maturation

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete


See also

References

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