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The Journal of Neuroscience, August 15, 2002, 22(16):7016-7026

Spatial and Temporal Regulation of Ca²⁺/Calmodulin-Dependent Protein Kinase II Activity in Developing Neurons

Andrea Menegon¹, Claudia Verderio², Chiara Leoni¹, Fabio Benfenati³, Andrew J. Czernik⁴, Paul Greengard⁴, Michela Matteoli², and Flavia Valtorta¹

¹ Department of Neuroscience, S. Raffaele Scientific Institute and "Vita-Salute" University, 20132 Milano, Italy, ² Department of Medical Pharmacology, Consiglio Nazionale delle Ricerche Cellular and Molecular Pharmacology Center, 20129 Milano, Italy, ³ Department of Experimental Medicine, Section of Physiology, University of Genova, 16132 Genova, Italy, and ⁴ Laboratory of Molecular Cellular Neuroscience, The Rockefeller University, New York, New York 10021

We have studied Ca²⁺/calmodulin-dependent protein kinase II (CaMKII) isoform distribution and activity in embryonic hippocampal neurons developing in culture. We have found a strong correlation between the expression of the  subunit of the enzyme and the ability to undergo depolarization-dependent phosphorylation, which in young neurons is limited to the somatodendritic pool of the kinase. The lack of responsiveness of the axons of young CaMKII-positive neurons is not caused by a lower Ca²⁺ influx but rather by a differential balance between kinase and phosphatase activities in this compartment. After the establishment of synaptic contacts, the presynaptic pool of the kinase displays an increasing level of activity and acquires the parallel ability to phosphorylate synapsin I, which represents one of the major CaMKII presynaptic targets in mature nerve terminals. In contrast, the activity of the postsynaptic pool of the kinase remains constant throughout synaptogenesis. In the presence of a nearly homogeneous subcellular distribution, this highly regionalized regulation of activity may reflect the multifunctional roles of CaMKII in both developing and mature neurons.

Key words: protein phosphorylation; neuronal differentiation; synapse; phosphospecific antibodies; hippocampal neurons; synapsin

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Copyright © 2002 Society for Neuroscience  0270-6474/02/22167016-11$05.00/0

This article has been cited by other articles:

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