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The Journal of Neuroscience, December 15, 2001, 21(24):9561-9571
Rapid Redistribution of the Postsynaptic Density Protein PSD-Zip45 (Homer 1c) and Its Differential Regulation by NMDA Receptors and Calcium Channels
Shigeo Okabe1, 2, 5, Tomoe Urushido1, Daijiro Konno3, Haruo Okado4, 5, and Kenji Sobue3 1 Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan, 2 Molecular Neurophysiology Group, Neuroscience Research Institute, National Institutes of Advanced Industrial Science and Technology, Tsukuba, Ibaraki, 305-8566, Japan, 3 Division of Neurochemistry and Neuropharmacology, Department of Neuroscience, Biomedical Research Center, Osaka University Graduate School of Medicine, Suita, Osaka, 565-0871, Japan, 4 Department of Neurobiology, Tokyo Metropolitan Institute for Neuroscience, Fuchu, Tokyo, 183-8526, Japan, and 5 Core Research for Evolution Science and Technology, Japan Science and Technology Corporation, Kawaguchi, 332-0012, Japan
PSD-Zip45 (Homer 1c) and PSD-95 are postsynaptic density (PSD) proteins containing distinct protein-interacting motifs. Green fluorescent protein (GFP)-tagged PSD-Zip45 and PSD-95 molecules were targeted to the PSD in hippocampal neurons. We analyzed dynamic behavior of these GFP-tagged PSD proteins by using time-lapse confocal microscopy. In contrast to the less dynamic properties of PSD-95, PSD-Zip45 showed rapid redistribution and a higher steady-state turnover rate. Differential stimulation protocols were found to alter the direction of PSD-Zip45 assembly-disassembly. Transient increases in intracellular Ca2+ by voltage-dependent Ca2+ channel activation induced PSD-Zip45 clustering. In contrast, NMDA receptor-dependent Ca2+ influx resulted in the disassembly of PSD-Zip45 clusters. Thus, neuronal activity differentially redistributes a specific subset of PSD proteins, which are important for localization of both surface receptors and intracellular signaling complexes.
Key words: postsynaptic density; PSD; green fluorescent protein; GFP; fluorescence microscopy; hippocampus; homer; metabotropic glutamate receptors; mGluRs
Copyright © 2001 Society for Neuroscience 0270-6474/01/21249561-11$05.00/0
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