Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150

Swayze, Richard D.; Lisé, Marie-France; Levinson, Joshua N.; Phillips, Anthony G.; El-Husseini, Alaa

doi:10.1016/j.neuropharm.2004.07.014

Cited by 54 publications

(60 citation statements)

References 44 publications

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“…Western blot signals were detected with the Odyssey machine (Li-Cor) using infrared-conjugated antibodies as previously described (31) or by ECL (Amersham Biosciences).…”

Section: Methodsmentioning

confidence: 99%

ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms

Krivosheya

Tapia

Levinson

et al. 2008

Journal of Biological Chemistry

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102

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Perturbations in neuregulin-1 (NRG1)/ErbB4 function have been associated with schizophrenia. Affected patients exhibit altered levels of these proteins and display hypofunction of glutamatergic synapses as well as altered neuronal circuitry. However, the role of NRG1/ErbB4 in regulating synapse maturation and neuronal process formation has not been extensively examined. Here we demonstrate that ErbB4 is expressed in inhibitory interneurons at both excitatory and inhibitory postsynaptic sites. Overexpression of ErbB4 postsynaptically enhances size but not number of presynaptic inputs. Conversely, knockdown of ErbB4 using shRNA decreases the size of presynaptic inputs, demonstrating a specific role for endogenous ErbB4 in synapse maturation. Using ErbB4 mutant constructs, we demonstrate that ErbB4-mediated synapse maturation requires its extracellular domain, whereas its tyrosine kinase activity is dispensable for this process. We also demonstrate that depletion of ErbB4 decreases the number of primary neurites and that stimulation of ErbB4 using a soluble form of NRG1 results in exuberant dendritic arborization through activation of the tyrosine kinase domain of ErbB4 and the phosphoinositide 3-kinase pathway. These findings demonstrate that NRG1/ErbB4 signaling differentially regulates synapse maturation and dendritic morphology via two distinct mechanisms involving trans-synaptic signaling and tyrosine kinase activity, respectively.Although central nervous system synapses utilize a variety of brain-specific molecules to mediate contact formation and maturation, some of the proteins implicated in this process are also major players in neuromuscular junction development. Among these shared molecules are NRG1 3 and its receptor, ErbB4, which are expressed in both the developing and adult brain. Neuregulins comprise a family of four related genes (nrg1-4), each producing a large number of isoforms via differential promoter usage and alternative splicing (1, 2). NRGs contain EGF-like repeats, which enable them to bind to and activate EGF family receptors (ErbB2-4). Previous studies showed that NRG1 is initially synthesized as a transmembrane protein, which then undergoes proteolytic processing, whereby the extracellular EGF-containing fragment is released into the extracellular environment. The remaining intracellular fragment has been shown to translocate into the nucleus, where it regulates neuronal survival and transcription of PSD-95 (3, 4). Proteolytic processing of NRG1 is also regulated by neuronal activity and by interaction with ErbB receptors (3, 5). NRG1 is widely expressed throughout development and adulthood, with the highest expression in nervous tissue (6) and is essential for survival. In the central nervous system NRG1 is also required for differentiation, migration, and development of neurons and glia as well as for axonal myelination and pathfinding, dendritic development, and neurotransmitter receptor maintenance. During development, NRG1-ErbB signaling mediates radial glia maintenance and elonga...

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“…Western blot signals were detected with the Odyssey machine (Li-Cor) using infrared-conjugated antibodies as previously described (31) or by ECL (Amersham Biosciences).…”

Section: Methodsmentioning

confidence: 99%

ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms

Krivosheya

Tapia

Levinson

et al. 2008

Journal of Biological Chemistry

Self Cite

102

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“…Cells were washed 3 times with phosphatebuffered saline containing 0.3% Triton-X-100 before and after each antibody incubation. The following primary antibodies were used (immunoreactivity and dilution as indicated): GluR1 (rabbit, 1:1000; Upstate Biotechnology); GluR2/3 (rabbit, 1:1000; Chemicon Interna- (30).…”

Section: Methodsmentioning

confidence: 99%

Involvement of Myosin Vb in Glutamate Receptor Trafficking

Lisé

Wong

Trinh

et al. 2006

Journal of Biological Chemistry

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118

107

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Myosin V motors mediate cargo transport; however, the identity of neuronal molecules transported by these proteins remains unknown. Here we show that myosin Vb is expressed in several neuronal populations and associates with the ␣-amino-3-hydroxy-5-methyl-4-isoxazole propionate-type glutamate receptor subunit GluR1. In developing hippocampal neurons, expression of the tail domain of myosin Vb, but not myosin Va, enhanced GluR1 accumulation in the soma and reduced its surface expression. These changes were accompanied by reduced GluR1 clustering and diminished frequency of excitatory but not inhibitory synaptic currents. Similar effects were observed upon expression of full-length myosin Vb lacking a C-terminal region required for binding to the small GTPase Rab11. In contrast, mutant myosin Vb did not change the localization of several other neurotransmitter receptors, including the glutamate receptor subunit NR1. These results reveal a novel mechanism for the transport of a specific glutamate receptor subunit in neurons mediated by a member of the myosin V family.Proper sorting and transport of excitatory neurotransmitter receptors and associated proteins is essential for neuronal activity and plasticity. Recent studies have identified several proteins that regulate clustering of neurotransmitter receptors at the synapse (1). However, it remains unknown what proteins mediate sorting and delivery of receptors from the soma to postsynaptic sites. Molecular motors that regulate cargo trafficking on both actin filaments and microtubules have been implicated in initial transport and delivery to specific subcellular sites (2, 3). In particular, class V of unconventional myosins is actin-based motors thought to regulate trafficking of organelles and associated proteins in neuronal cells (2, 4).Three known members of the myosin V family have been detected in brain extracts. The most studied member, myosin Va, is widely expressed in the brain (5). Dilute mice, which possess mutation in the myosin Va gene, suffer from impaired melanosome transport and severe seizures and die within 2-3 weeks after birth (6). These observations suggest that alteration in the transport of important yet unknown cargos contributed to the observed defects in neuronal function. In neurons, myosin Va is enriched at the postsynaptic density (PSD) 4 of excitatory synapses (7) and associates with the scaffolding guanylate kinase domain-associated protein through interaction with the dynein light chain (8). The association of guanylate kinase domain-associated protein with the postsynaptic density protein-95 (PSD-95), a protein involved in glutamate receptor clustering, may functionally couple these proteins to myosin Va (1, 9).Myosin Vb and myosin Vc are two additional members of the myosin V family that are also expressed in the brain; however, their exact localization in neurons remains unclear (10, 11). All of these motors share ϳ42% identity and contain a conserved N-terminal motor domain followed by a coiled-coil region and a globular C-termi...

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“…S4, available at www.jneurosci.org as supplemental material). Although it is possible that eNRG1 treatment also enhanced the channel gating activity of AMPA receptors by inducing receptor phosphorylation (Swayze et al, 2004), no significant changes in Ser 845 phosphorylation of GluA1 were observed in eNRG1-treated animals (supplemental Fig. S5, available at www.jneurosci.org as supplemental material).…”

Section: Enrg1 Elevates Protein Levels and Synaptic Accumulation Of Amentioning

confidence: 99%

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

Abe¹,

Namba²,

Kato³

et al. 2011

J. Neurosci.

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Neuregulin-1 (NRG1) signaling is thought to contribute to both neuronal development and schizophrenia neuropathology. Here, we describe the developmental effects of excessive peripheral NRG1 signals on synaptic activity and AMPA receptor expression of GABAergic interneurons in postnatal rodent neocortex. A core peptide common to all NRG1 variants (eNRG1) was subcutaneously administered to mouse pups. Injected eNRG1 penetrated the blood-brain barrier and activated ErbB4 NRG1 receptors in the neocortex, in which ErbB4 mRNA is predominantly expressed by parvalbumin-positive GABAergic interneurons. We prepared neocortical slices from juvenile mice that were receiving eNRG1 subchronically and recorded inhibitory synaptic activity from layer V pyramidal neurons. Postnatal eNRG1 treatment significantly enhanced polysynaptic IPSCs, although monosynaptic IPSCs were not affected. Examination of excitatory inputs to parvalbumin-containing GABAergic interneurons revealed that eNRG1 treatment significantly increased AMPA-triggered inward currents and the amplitudes and frequencies of miniature EPSCs (mEPSCs). Similar effects on mEPSCs were observed in mice treated with a soluble, full-length form of NRG1 type I. Consistent with the electrophysiologic data, expression of the AMPA receptor GluA1 (i.e., GluR1, GluRA) was upregulated in the postsynaptic density/cytoskeletal fraction prepared from eNRG1-treated mouse neocortices. Cortical GABAergic neurons cultured with eNRG1 exhibited a significant increase in surface GluA1 immunoreactivity at putative synaptic sites on their dendrites. These results indicate that NRG1 circulating in the periphery influences postnatal development of synaptic AMPA receptor expression in cortical GABAergic interneurons and may play a role in conditions characterized by GABA-associated neuropathologic processes.

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Modulation of dopamine mediated phosphorylation of AMPA receptors by PSD-95 and AKAP79/150

Cited by 54 publications

References 44 publications

ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms

ErbB4-Neuregulin Signaling Modulates Synapse Development and Dendritic Arborization through Distinct Mechanisms

Involvement of Myosin Vb in Glutamate Receptor Trafficking

Neuregulin-1 Signals from the Periphery Regulate AMPA Receptor Sensitivity and Expression in GABAergic Interneurons in Developing Neocortex

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