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 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.

[1]  H. Okado,et al.  Spine Formation and Correlated Assembly of Presynaptic and Postsynaptic Molecules , 2001, The Journal of Neuroscience.

[2]  P. Worley,et al.  Dendritic and Axonal Targeting of Type 5 Metabotropic Glutamate Receptor Is Regulated by Homer1 Proteins and Neuronal Excitation , 2000, Journal of Neuroscience.

[3]  M. Kennedy,et al.  Signal-processing machines at the postsynaptic density. , 2000, Science.

[4]  J. H. Connor,et al.  Molecular memory by reversible translocation of calcium/calmodulin-dependent protein kinase II , 2000, Nature Neuroscience.

[5]  R. Malinow,et al.  Driving AMPA receptors into synapses by LTP and CaMKII: requirement for GluR1 and PDZ domain interaction. , 2000, Science.

[6]  K. Sobue,et al.  Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer 1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[7]  Y. Hata,et al.  Synamon, a Novel Neuronal Protein Interacting with Synapse-associated Protein 90/Postsynaptic Density-95-associated Protein* , 1999, The Journal of Biological Chemistry.

[8]  H. Okado,et al.  Alternative Splicing of the C-Terminal Domain Regulates Cell Surface Expression of the NMDA Receptor NR1 Subunit , 1999, The Journal of Neuroscience.

[9]  H. Okado,et al.  Continual remodeling of postsynaptic density and its regulation by synaptic activity , 1999, Nature Neuroscience.

[10]  T. Boeckers,et al.  Proline-Rich Synapse-Associated Protein-1/Cortactin Binding Protein 1 (ProSAP1/CortBP1) Is a PDZ-Domain Protein Highly Enriched in the Postsynaptic Density , 1999, The Journal of Neuroscience.

[11]  P. Worley,et al.  Shank, a Novel Family of Postsynaptic Density Proteins that Binds to the NMDA Receptor/PSD-95/GKAP Complex and Cortactin , 1999, Neuron.

[12]  K. Svoboda,et al.  Rapid spine delivery and redistribution of AMPA receptors after synaptic NMDA receptor activation. , 1999, Science.

[13]  K. Shen,et al.  Dynamic control of CaMKII translocation and localization in hippocampal neurons by NMDA receptor stimulation. , 1999, Science.

[14]  R. Huganir,et al.  Organization and regulation of proteins at synapses. , 1999, Current opinion in cell biology.

[15]  R. Nicoll,et al.  Rapid, Activation-Induced Redistribution of Ionotropic Glutamate Receptors in Cultured Hippocampal Neurons , 1999, The Journal of Neuroscience.

[16]  K. Sobue,et al.  Isolation of PSD‐Zip45, a novel Homer/vesl family protein containing leucine zipper motifs, from rat brain 1 , 1998, FEBS letters.

[17]  P. Worley,et al.  Homer Regulates the Association of Group 1 Metabotropic Glutamate Receptors with Multivalent Complexes of Homer-Related, Synaptic Proteins , 1998, Neuron.

[18]  S. Weed,et al.  Identification of a Novel Cortactin SH3 Domain-Binding Protein and Its Localization to Growth Cones of Cultured Neurons , 1998, Molecular and Cellular Biology.

[19]  D. Linden,et al.  Homer Binds a Novel Proline-Rich Motif and Links Group 1 Metabotropic Glutamate Receptors with IP3 Receptors , 1998, Neuron.

[20]  K. Inokuchi,et al.  Novel Members of the Vesl/Homer Family of PDZ Proteins That Bind Metabotropic Glutamate Receptors* , 1998, The Journal of Biological Chemistry.

[21]  S. Okabe,et al.  Survival and synaptogenesis of hippocampal neurons without NMDA receptor function in culture , 1998, The European journal of neuroscience.

[22]  M. Fischer,et al.  Rapid Actin-Based Plasticity in Dendritic Spines , 1998, Neuron.

[23]  A. Craig,et al.  Role of Actin in Anchoring Postsynaptic Receptors in Cultured Hippocampal Neurons: Differential Attachment of NMDA versus AMPA Receptors , 1998, The Journal of Neuroscience.

[24]  K. Inokuchi,et al.  vesl, a gene encoding VASP/Ena family related protein, is upregulated during seizure, long‐term potentiation and synaptogenesis 1 , 1997, FEBS letters.

[25]  Y. Takai,et al.  SAPAPs. A family of PSD-95/SAP90-associated proteins localized at postsynaptic density. , 1997, The Journal of biological chemistry.

[26]  C. Barnes,et al.  Homer: a protein that selectively binds metabotropic glutamate receptors , 1997, Nature.

[27]  M. Sheng,et al.  GKAP, a Novel Synaptic Protein That Interacts with the Guanylate Kinase-like Domain of the PSD-95/SAP90 Family of Channel Clustering Molecules , 1997, The Journal of cell biology.

[28]  R. Wenthold,et al.  Evidence for multiple AMPA receptor complexes in hippocampal CA1/CA2 neurons , 1996, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[29]  O. Garaschuk,et al.  Fractional Ca2+ currents through somatic and dendritic glutamate receptor channels of rat hippocampal CA1 pyramidal neurones. , 1996, The Journal of physiology.

[30]  A. Sparks,et al.  Distinct ligand preferences of Src homology 3 domains from Src, Yes, Abl, Cortactin, p53bp2, PLCgamma, Crk, and Grb2. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[31]  Y. Kanegae,et al.  Efficient generation of recombinant adenoviruses using adenovirus DNA-terminal protein complex and a cosmid bearing the full-length virus genome. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[32]  S. Sugano,et al.  Efficient gene activation in mammalian cells by using recombinant adenovirus expressing site-specific Cre recombinase. , 1995, Nucleic acids research.

[33]  P. Seeburg,et al.  Domain interaction between NMDA receptor subunits and the postsynaptic density protein PSD-95. , 1995, Science.

[34]  D. Johnston,et al.  Different Ca2+ channels in soma and dendrites of hippocampal pyramidal neurons mediate spike-induced Ca2+ influx. , 1995, Journal of neurophysiology.

[35]  H. Markram,et al.  Dendritic calcium transients evoked by single back‐propagating action potentials in rat neocortical pyramidal neurons. , 1995, The Journal of physiology.

[36]  Y. Kanegae,et al.  A simple and efficient method for purification of infectious recombinant adenovirus. , 1994, Japanese journal of medical science & biology.

[37]  N. Hirokawa,et al.  Dynamics of the neuronal intermediate filaments , 1993, The Journal of cell biology.

[38]  B. Voss,et al.  SAP90, a rat presynaptic protein related to the product of the Drosophila tumor suppressor gene dlg-A. , 1993, The Journal of biological chemistry.

[39]  J. Parsons,et al.  Cortactin, an 80/85-kilodalton pp60src substrate, is a filamentous actin-binding protein enriched in the cell cortex , 1993, The Journal of cell biology.

[40]  D. Tank,et al.  Calcium concentration dynamics produced by synaptic activation of CA1 hippocampal pyramidal cells , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[41]  M. Kennedy,et al.  The rat brain postsynaptic density fraction contains a homolog of the drosophila discs-large tumor suppressor protein , 1992, Neuron.

[42]  N. Hirokawa,et al.  Differential behavior of photoactivated microtubules in growing axons of mouse and frog neurons , 1992, The Journal of cell biology.

[43]  Yamamura Ken-ichi,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector , 1991 .

[44]  H. Niwa,et al.  Efficient selection for high-expression transfectants with a novel eukaryotic vector. , 1991, Gene.

[45]  N. Hirokawa,et al.  Actin dynamics in growth cones , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[46]  M. Sheng,et al.  PDZ domains and the organization of supramolecular complexes. , 2001, Annual review of neuroscience.

[47]  田所 智子.  Involvement of unique leucine-zipper motif of PSD-Zip45 (Homer1c/vesl-1L) in group 1 metabotropic glutamate receptor clustering , 2000 .

[48]  S. Palay.  The morphology of synapses in the central nervous system. , 1958, Experimental cell research.

[49]  G. Palade,et al.  Electron microscope observations of interneuronal and neuromuscular synapses , 1954 .

[50]  P. S. Chen.  The rate of oxygen consumption in the lethal hybrid between Triton and Salamandra. , 1953, Experimental cell research.