Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

Konradi, Christine; Macı́as, Wendy; Dudman, Joshua T.; Carlson, Richard R.

doi:10.1016/s0169-328x(03)00204-3

Cited by 6 publications

(5 citation statements)

References 24 publications

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“…3) and D1 DA receptor activation (Fig. 5b), consistent with reports that Ca v s are necessary for glutamate-induced c-fos expression in striatal neurons (Rajadhyaksha et al, 1999) and forskolin-induced proenkephalin gene expression in rat striatal neurons (Konradi et al, 2003). However, block of Ca v s did not affect forskolin-induced aspartate release (Fig.…”

Section: Discussionsupporting

confidence: 91%

Autocrine Activation of Neuronal NMDA Receptors by Aspartate Mediates Dopamine- and cAMP-Induced CREB-Dependent Gene Transcription

Almeida

Murray²,

Zielke³

et al. 2009

J. Neurosci.

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cAMP can stimulate the transcription of many activity-dependent genes via activation of the transcription factor, cAMP response element-binding protein (CREB). However, in mouse cortical neuron cultures, prior to synaptogenesis, neither cAMP nor dopamine, which acts via cAMP, stimulated CREB-dependent gene transcription when NR2B-containing NMDA receptors (NMDARs) were blocked. Stimulation of transcription by cAMP was potentiated by inhibitors of excitatory amino acid uptake, suggesting a role for extracellular glutamate or aspartate in cAMP-induced transcription. Aspartate was identified as the extracellular messenger: enzymatic scavenging of L-aspartate, but not glutamate, blocked stimulation of CREB-dependent gene transcription by cAMP; moreover, cAMP induced aspartate but not glutamate release. Together, these results suggest that cAMP acts via an autocrine or paracrine pathway to release aspartate, which activates NR2B-containing NMDARs, leading to Ca 2ϩ entry and activation of transcription. This cAMP/aspartate/NMDAR signaling pathway may mediate the effects of transmitters such as dopamine on axon growth and synaptogenesis in developing neurons or on synaptic plasticity in mature neural networks.

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Section: Discussionsupporting

confidence: 91%

Autocrine Activation of Neuronal NMDA Receptors by Aspartate Mediates Dopamine- and cAMP-Induced CREB-Dependent Gene Transcription

Almeida

Murray²,

Zielke³

et al. 2009

J. Neurosci.

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“…The Gs-protein-coupled D1 receptor activates adenylate cyclase, followed by increased cAMP formation and activation of protein kinase A (PKA) in many cell lines and neurons (Neve et al, 2004). In striatal neurons, the cAMP/PKA system is among important pathways mediating inducible gene expression (Konradi et al, 2003). Thus, PKA was speculated to be a first candidate to play a significant role in dopamine-stimulated Homer1a expression.…”

Section: Resultsmentioning

confidence: 99%

“…Thus, CREB could be a transcription factor mediating the phasic Homer1a expression. Phosphorylation of CREB is a needed chemical process for activating this factor to facilitate D1 receptor-dependent gene expression in striatal neurons (Simpson et al, 1995;Konradi et al, 2003). Cytosolic second messengers (Ca 2ϩ ions, PKA, and CaMKs) also phosphorylate CREB to facilitate target gene transcription in heterologous systems and cultured neurons (Lonze and Ginty, 2002;Carlezon et al, 2005).…”

Section: Discussionmentioning

confidence: 99%

In Vivo Regulation of Homer1a Expression in the Striatum by Cocaine

et al. 2007

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The glutamate receptor adaptor protein Homer is concentrated in the postsynaptic density of excitatory synapses and is critical for normal operation of synaptic transmission. In this study, we investigated the responsiveness of Homer family proteins to dopamine stimulation with the psychostimulant cocaine in rat striatal neurons both in vivo and in vitro. We found that a single dose of cocaine specifically induced a rapid and transient increase in protein levels of the Homer1a, but not Homer1b/c and Homer2a/b, isoforms in the striatum. This selective Homer1a induction was mediated primarily through activation of dopamine D1, but not D2, receptors. Both protein kinase A and Ca 2ϩ /calmodulin-dependent protein kinases are important for mediating the cocaine stimulation of Homer1a expression. At the transcriptional level, cAMP response element-binding protein serves as a prime transcription factor transmitting the signals derived from D1 receptors and associative pathways to the CaCRE sites within the Homer1a promoter. From a functional perspective, non-cross-linking Homer1a, once induced, competed with the cross-linking isoforms of Homer proteins (Homer1b/c and Homer2a/b) to uncouple the connection of group I metabotropic glutamate receptors (mGluRs) with inositol-1,4,5-triphosphate receptors. These results indicate that cocaine possesses the ability to stimulate Homer1a expression in striatal neurons through a specific synapse-to-nucleus pathway. Moreover, inducible Homer1a expression may represent a transcription-dependent mechanism underlying the dynamic regulation of submembranous macromolecular complex formation between group I mGluRs and their anchoring proteins.Synaptic Homer proteins are important for synaptic construction and function Sheng and Kim, 2002). Long-form Homer proteins (Homer1b/c, Homer2a/b, and Homer3) contain the N-terminal EVH1 (Enabled/ VASP homology 1) domain, which binds the C terminus of group I metabotropic glutamate receptors (mGluRs), whereas the C-terminal coiled-coil structure and leucine zipper motifs render a capability for self-assembly (Brakeman et al., 1997;Xiao et al., 1998;Xiao et al., 2000). Thus, as a prominent scaffolding molecule concentrated in the postsynaptic density of excitatory synapses, Homer crosslinks group I mGluRs to other targets in a specific subcellular microdomain to regulate a specific signaling activity. Emerging evidence indicates that Homer proteins play an essential role in the membrane trafficking of mGluR1␣/5 (Ango et al., 2000); the coupling of mGluR1/5 to inositol-1,4,5-triphosphate (IP 3 ) receptors and the cation (Ca 2ϩ or K ϩ ) channel (Yuan et al., 2003); the development of spines, axons, and synapses (Shiraishi et al., 2003); and drug addiction (Swanson et al., 2001;Szumlinski et al., 2004Szumlinski et al., , 2005; also see below).One distinctive member of Homer family is Homer1a (Brakeman et al., 1997;Xiao et al., 1998Xiao et al., , 2000. Unlike the long-form of Homer proteins, this short-form of Homer lacks the C-terminal coiled-co...

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“…17␤-E2 could also act at the level of membrane-associated ERs and crosstalk with others signaling pathways such as CREB protein to induce its effect on PPE expression. Indeed, CREB response element is present in the promoter of PPE gene [88].…”

Section: Implication Of Er␣ and Er␤ In Neuromodulationmentioning

confidence: 99%

Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain

Morissette

Saux

D’Astous

et al. 2008

The Journal of Steroid Biochemistry and Molecular Biology

161

137

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Striatal proenkephalin gene induction: coordinated regulation by cyclic AMP and calcium pathways

Cited by 6 publications

References 24 publications

Autocrine Activation of Neuronal NMDA Receptors by Aspartate Mediates Dopamine- and cAMP-Induced CREB-Dependent Gene Transcription

Autocrine Activation of Neuronal NMDA Receptors by Aspartate Mediates Dopamine- and cAMP-Induced CREB-Dependent Gene Transcription

In Vivo Regulation of Homer1a Expression in the Striatum by Cocaine

Contribution of estrogen receptors alpha and beta to the effects of estradiol in the brain

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