A GluR1-cGKII Interaction Regulates AMPA Receptor Trafficking

Serulle, Yafell; Zhang, Shuang; Ninan, Ipe; Puzzo, Daniela; McCarthy, Maria; Khatri, Latika; Arancio, Ottavio; Ziff, Edward B.

doi:10.1016/j.neuron.2007.09.016

Cited by 167 publications

(206 citation statements)

References 74 publications

(100 reference statements)

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“…19 Accordingly, we also investigated NO-dependent GluR1 phosphorylation at S845, a protein modification that increases GluR1 surface expression. 20 After stretch þ NMDA, phosphorylated GluR1 increased to 302 ± 47.6% of control levels (Po0.05, Figure 4a). Notably, cells treated with an NR2b antagonist did not exhibit a significant increase in phosphorylated GluR1 relative to control cultures (P ¼ 0.15, Figure 4a).…”

Section: Resultsmentioning

confidence: 94%

PICK1-mediated GluR2 endocytosis contributes to cellular injury after neuronal trauma

Bell

Park

et al. 2009

Cell Death Differ

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Constitutive and activity-dependent regulation of the AMPA receptor GluR2 content is recognized as an important mediator of both neuronal plasticity and vulnerability to excitotoxic neuron death. In the latter case, inclusion of GluR2 protects against glutamate excitotoxicity in CNS disease by lowering receptor single-channel conductance and preventing deleterious calcium influx. We investigated the hypothesis that aberrations in GluR2 trafficking after in vitro and in vivo cerebral trauma contribute to excitotoxicity and associated calcium-dependent cell death processes. First, in an in vitro model of traumatic brain injury (TBI), we observed PICK1 and N-methyl-D-aspartic acid (NMDA) receptor-dependent phosphorylation and internalization of GluR2. The contributing cell signaling mechanisms involved enhanced binding between PKCa (the kinase that phosphorylates GluR2) and PICK1 (its PDZ-binding partner), and a novel protein interaction between PKCa and the NMDA receptor scaffolding protein PSD-95. Functionally, these phenomena enhanced single cell AMPAR mEPSCs and protracted calcium extrusion. In vivo TBI similarly promoted GluR2 phosphorylation and internalization, with enhanced expression of calcium-permeable AMPARs in the injured hippocampus. Peptide-mediated perturbation of the PKCa/PICK1 protein interaction after trauma preserved surface GluR2 expression, attenuated AMPAR-mediated toxicity, and occluded the sensitivity of neuronal physiology to calcium-permeable AMPAR antagonists. These findings suggest that experimental TBI promotes the expression of injurious GluR2-lacking AMPARs, thereby enhancing cellular vulnerability to secondary excitotoxicity. Traumatic brain injury (TBI) continues to be a leading cause of morbidity and disability in North America. 1 At the cellular level, excitotoxic stimulation of N-methyl-D-aspartate (NMDA) and a-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) glutamatergic receptors has a major function in the deregulation of calcium homeostasis and acute cell swelling after TBI, ultimately leading to secondary neuronal cell death hours to days after the primary injury. 1 Unfortunately, global antagonism of these ionotropic channels (which has generally targeted the highly calciumpermeable NMDARs) is a clinically impractical approach because of interference with physiological receptor function. 2 As such, it remains of critical importance to identify novel potential intracellular targets of anti-excitotoxic therapy to mitigate delayed secondary cell loss, and improve functional outcome after TBI.Physiologically, AMPA receptors mediate the majority of excitatory ionotropic neurotransmission in the CNS. 3 Pathologically, however, AMPA receptors can also mediate excitotoxic neuronal damage when GluR2 subunits are absent from the tetrameric receptor complex 4 (composed of four subunits, GluR1-4). This is because receptors devoid of the GluR2 subunit (e.g. homomers of GluR1) exhibit two-to three-fold increases in single-channel conductance, increased calcium and zinc permeab...

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Section: Resultsmentioning

confidence: 94%

PICK1-mediated GluR2 endocytosis contributes to cellular injury after neuronal trauma

Bell

Park

et al. 2009

Cell Death Differ

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“…*Po0.05, **Po0.01, ***Po0.001 in relation to pLKO in figures (b-l); # Po0.05, ## Po0.01, ### Po0.001 in relation to pLKO with SNAP in figures (b and c, e-g, j-l); N ¼ 3-4, one-way ANOVA addition, cGKII activity has been shown to modulate the trafficking of AMPA receptors and LTP in a cGMP-dependent manner in hippocampal slices. 20 Nonetheless, cGK activation has been shown to promote neuronal cell death in a mouse model of retinitis pigmentosa. 46 We have shown that cGKII precisely controls neuronal survival as a downstream relay for NO in the retina.…”

Section: Discussionmentioning

confidence: 99%

“…In hippocampal neurons, cGKI has been implicated in activity-dependent presynaptic potentiation 19 and cGKII regulates AMPA receptors trafficking at the postsynaptic neuron. 20 Pre-and postsynaptic actions of cGKs may involve a parallel activation of the small GTPase RhoA in the regulation of actin cytoskeleton, which contributes to synaptic strengthening in hippocampal neurons. 21 In the developing retina, cGKs have been associated with Src avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog (Src)-induced neuronal apoptosis, 15 ascorbate transport 14 and cGKII, specifically, regulates V-Akt murine thymoma viral oncogene (AKT)/PKB activation.…”

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confidence: 99%

The nitric oxide-cGKII system relays death and survival signals during embryonic retinal development via AKT-induced CREB1 activation

et al. 2014

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During early neurogenesis, retinal neuronal cells display a conserved differentiation program in vertebrates. Previous studies established that nitric oxide (NO) and cGMP accumulation regulate essential events in retinal physiology. Here we used pharmacological and genetic loss-of-function to investigate the effects of NO and its downstream signaling pathway in the survival of developing avian retinal neurons in vitro and in vivo. Six-day-old (E6) chick retinal cells displayed increased calcium influx and produced higher amounts of NO when compared with E8 cells. L-arginine (substrate for NO biosynthesis) and S-nitroso-N-acetyl-D,L-penicillamine (SNAP; a nitrosothiol NO donor) promoted extensive cell death in E6 retinas, whereas in E8 both substances decreased apoptosis. The effect of NO at both periods was mediated by soluble guanylyl cyclase (sGC) and cGMP-dependent kinase (cGK) activation. In addition, shRNA-mediated cGKII knockdown prevented NO-induced cell death (E6) and cell survival (E8). This, NO-induced cell death or cell survival was not correlated with an early inhibition of retinal cell proliferation. E6 cells also responded differentially from E8 neurons regarding cyclic AMP-responsive element-binding protein (CREB) activation in the retina in vivo. NO strongly decreased nuclear phospho-CREB staining in E6 but it robustly enhanced CREB phosphorylation in the nuclei of E8 neurons, an effect that was completely abrogated by cGKII shRNAs at both embryonic stages. The ability of NO in regulating CREB differentially during retinal development relied on the capacity of cGKII in decreasing (E6) or increasing (E8) nuclear AKT (V-Akt murine thymoma viral oncogene) activation. Accordingly, inhibiting AKT prevented both cGKII shRNA-mediated CREB upregulation in E6 and SNAP-induced CREB activation in E8. Furthermore, shRNAmediated in vivo cGKII or in vitro CREB1 knockdown confirmed that NO/cGKII dualistically regulated the downstream CREB1 pathway and caspase activation in the chick retina to modulate neuronal viability. These data demonstrate that NO-mediated cGKII signaling may function to control the viability of neuronal cells during early retinal development via AKT/CREB1 activity. Cell Death and Differentiation (2014) 21, 915-928; doi:10.1038/cdd.2014.11; published online 14 February 2014The retina is part of the central nervous system (CNS) because of its derivation from the anterior neural tube. Mature retinal tissue is arranged in a laminar structure composed of seven major classes of cells: ganglion, horizontal, amacrine, bipolar, cone and rod photoreceptors and the Mü ller glia. 1 Early retinal tissue is a pseudo-stratified epithelium in which mitotically active neuronal precursor cells are found. Another noteworthy characteristic of vertebrate retinogenesis is the well-established chronology of cell-type generation, with ganglion cells generally being the first cells to be born and the Mü ller glia and bipolar neurons usually the last. Nevertheless, the differentiation periods of different cell type...

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“…Taken together, these evidences suggest that GluR1 phosphorylation of Ser845 delivers AMPARs to the plasma membrane, being the influx of Ca 2ϩ through NMDA receptors necessary for the diffusion of the receptors until they reach the synapse, promoting synaptic potentiation (Oh et al, 2006). A recent study showed that GluR1 phosphorylation at Ser845 may also be accomplished by cGKII, which complements the PKA-induced surface increase of GluR1 (Serulle et al, 2007). The delivery of GluR1-containing AMPARs to the synapse and/or their stabilization in the synaptic compartment may also depend on the phosphorylation at Ser818 by PKC and on the CaMKII-dependent phosphorylation of a PDZ domain containing substrate that remains to be identified .…”

Section: Role Of Ampars In Ltpmentioning

confidence: 93%

“…2). GluR1 subunit has been described to be phosphorylated at three serine residues located in the intracellular C-terminus: serine 831 (Ser831) can be phosphorylated by both protein kinase C (PKC) (Roche et al, 1996) and CaMKII (Mammen et al, 1997); serine 845 (Ser845) is a protein kinase A (PKA) and cGMP-dependent protein kinase II (cGKII) phosphorylation site (Roche et al, 1996;Serulle et al, 2007) and serine 818 (Ser818) is a substrate for PKC (Fig. 1B) .…”

Section: Ampar Post-translational Modificationsmentioning

confidence: 99%