Rapid redistribution of the postsynaptic density protein PSD-Zip45 (Homer 1c) and its differential regulation by NMDA receptors and calcium channels.
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 Ca(2+) by voltage-dependent Ca(2+) channel activation induced PSD-Zip45 clustering. In contrast, NMDA receptor-dependent Ca(2+) 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.
Okabe
S
S
Department of Anatomy and Cell Biology, School of Medicine, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, 113-8519, Japan. okabe.cbio@tmd.ac.jp
Urushido
T
T
Konno
D
D
Okado
H
H
Sobue
K
K
D000818:Animals; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000378:metabolism; D000076122:Disks Large Homolog 4 Protein; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D006624:Hippocampus; D000072233:Homer Scaffolding Proteins; D007424:Intracellular Fluid / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins / Q000235:genetics; D046911:Macromolecular Substances; D008565:Membrane Proteins; D051379:Mice; D018613:Microscopy, Confocal; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D013268:Stimulation, Chemical; D013569:Synapses / Q000378:metabolism*
D015220:Calcium Channels; D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D018691:Excitatory Amino Acid Antagonists; D000072233:Homer Scaffolding Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008164:Luminescent Proteins; D046911:Macromolecular Substances; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D016194:Receptors, N-Methyl-D-Aspartate; D011993:Recombinant Fusion Proteins; C033652:postsynaptic density proteins; D002104:Cadmium; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases; D002118:Calcium