Selective regulation of neurite extension and synapse formation by the beta but not the alpha isoform of CaMKII.
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.
Fink
Charles C
CC
Department of Molecular Pharmacology, Stanford University Medical School, Stanford, CA 94305, USA.
Bayer
Karl-Ulrich
KU
Myers
Jason W
JW
Ferrell
James E
JE
Schulman
Howard
H
Meyer
Tobias
T
D000199:Actins / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000378:metabolism; D001596:Benzylamines; D001665:Binding Sites; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000145:classification / Q000235:genetics / Q000502:physiology*; D002458:Cell Fractionation / Q000379:methods; D002465:Cell Movement; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D049452:Green Fluorescent Proteins; D015151:Immunoblotting; D007150:Immunohistochemistry; D007546:Isoquinolines / Q000378:metabolism; D008164:Luminescent Proteins / Q000378:metabolism; D018613:Microscopy, Confocal; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000378:metabolism; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D020033:Protein Isoforms / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D013449:Sulfonamides; D013569:Synapses / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors; D014162:Transfection
D000199:Actins; D001426:Bacterial Proteins; D001596:Benzylamines; D004791:Enzyme Inhibitors; D007546:Isoquinolines; C425780:KN 92; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D020033:Protein Isoforms; D013449:Sulfonamides; C033652:postsynaptic density proteins; C054562:yellow fluorescent protein, Bacteria; D049452:Green Fluorescent Proteins; C017475:lucifer yellow; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases