Synaptic concentration of type‐I adenylyl cyclase in cerebellar neurons

Wang, Hongbing; Chan, Guy C.‐K.; Athos, Jaime; Storm, Daniel R.

doi:10.1046/j.1471-4159.2002.01206.x

Cited by 14 publications

(15 citation statements)

References 35 publications

(43 reference statements)

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“…Either AC1 or AC8 can provide the cAMP signal required for L-LTP (Wong et al, 1999). LTP at the parallel fiber/Purkinje cell synapse is completely ablated in AC1 Ϫ/Ϫ mice , which probably reflects the concentration of AC1 at these excitatory synapses (Wang et al, 2002). In contrast, we show that mossy fiber LTP depends on both AC1 and AC8.…”

Section: Discussionmentioning

confidence: 57%

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Type 8 Adenylyl Cyclase Is Targeted to Excitatory Synapses and Required for Mossy Fiber Long-Term Potentiation

et al. 2003

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Mossy fiber/CA3 long-term potentiation (LTP) is hypothesized to depend on cAMP signals generated by Ca 2ϩ -stimulated adenylyl cyclases AC1 or AC8. AC1 gene knock-out mice (AC1 Ϫ/Ϫ ) show a partial reduction in mossy fiber LTP, suggesting that either AC8 activity is also critical for mossy fiber LTP or that there is a component of mossy fiber LTP that is independent of CaM-activated adenylyl cyclases. To address this issue, mossy fiber LTP was examined in hippocampal slices from AC8 Ϫ/Ϫ and AC1 Ϫ/Ϫ ϫ AC8 Ϫ/Ϫ double knock-out mice (DKO). Despite the fact that AC8 contributes only a small fraction of the Ca 2ϩ -stimulated adenylyl cyclase activity in the hippocampus and is less sensitive to Ca 2ϩ than AC1, AC8 Ϫ/Ϫ mice exhibited mossy fiber LTP defects comparable with AC1 Ϫ/Ϫ and DKO mice. Furthermore, short-term plasticity was disrupted in AC8 Ϫ/Ϫ mice but not in AC1 Ϫ/Ϫ mice. Because AC1 is not localized at the excitatory synapses in hippocampal neurons, we hypothesized that AC8 may be targeted to synapses, in which higher synaptic-specific Ca 2ϩ increases occur. Here, we report that AC8 accumulates in puncta of dendrites and axons in hippocampal neurons and colocalizes with synaptic marker proteins. These data indicate that both synaptic and nonsynaptic cAMP signals, generated by different Ca 2ϩ -stimulated adenylyl cyclases, are required for mossy fiber LTP.

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Section: Discussionmentioning

confidence: 57%

“…5B). Comparable results were obtained when HA-tagged AC1 was expressed in HEK293 cells (Wang et al, 2002).…”

Section: Ha-tagged Ac8 Is Catalytically Activementioning

confidence: 71%

Type 8 Adenylyl Cyclase Is Targeted to Excitatory Synapses and Required for Mossy Fiber Long-Term Potentiation

et al. 2003

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“…Neuronal adenylyl cyclases such as types 1 and 8 have been identified to localize to neuronal membranes including post-synaptic densities (60,61) and thus presumably co-localize to a large degree with AKAP79/150 in these neurons. Interestingly, certain stimuli such as brief NMDA receptor stimulations can lead to a long lasting translocation of the AKAP79/150 complex and anchored PKA away from membranes and post-synaptic sites toward the cytosol (62).…”

Section: Resultsmentioning

confidence: 99%

Imaging CREB Activation in Living Cells

Friedrich¹,

Aramuni²,

Mank

et al. 2010

Journal of Biological Chemistry

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The Ca 2؉ -and cAMP-responsive element-binding protein (CREB) and the related ATF-1 and CREM are stimulus-inducible transcription factors that link certain forms of cellular activity to changes in gene expression. They are attributed to complex integrative activation characteristics, but current biochemical technology does not allow dynamic imaging of CREB activation in single cells. Using fluorescence resonance energy transfer between mutants of green fluorescent protein we here develop a signal-optimized genetically encoded indicator that enables imaging activation of CREB due to phosphorylation of the critical serine 133. The indicator of CREB activation due to phosphorylation (ICAP) was used to investigate the role of the scaffold and anchoring protein AKAP79/ 150 in regulating signal pathways converging on CREB. We show that disruption of AKAP79/150-mediated protein kinase A anchoring or knock-down of AKAP150 dramatically reduces the ability of protein kinase A to activate CREB. In contrast, AKAP79/150 regulation of CREB via L-type channels may only have minor importance. ICAP allows dynamic and reversible imaging in living cells and may become useful in studying molecular components and cell-type specificity of activity-dependent gene expression.Changes in gene expression are a hallmark of long term adaptive processes in many cell types and are crucially involved in the conversion from short term to long term plasticity of neuronal circuits. Transcription factors of the cAMP-responsive element-binding protein (CREB) 3 family have a prominent role in affecting such processes in various tissues and cell types (1-5). The family includes the homologous proteins CREB (6, 7), ATF-1 (8), and CREM (9). Upon stimulation a number of kinases phosphorylate the critical serine 133 residue within the kinase-inducible domain (KID) of CREB and the related transcription factors ATF-1 and CREM. Serine 133 phosphorylation leads to the recruitment of transcriptional coactivators, like CBP or its paralogue P300 that bind to the KID via the KID interaction domain (KIX) (10, 11). Interaction of CREB with CBP/P300 results in the assembly of the RNA-polymerase complex and in the expression of a large number of genes. Serine 133 phosphorylation is generally accepted as a key event in transcriptional regulation necessary although not in all cases sufficient, for CREB-mediated gene expression. Many studies focused on examining spatiotemporal profiles of CREB activation in cells and tissues by immunostainings using antibodies specific for serine 133 phosphorylation (for a selection, see Refs. 12-17). Few attempts were made to develop assays for real time imaging of CREB, a prerequisite for thorough analysis of the physiological events and the molecular dissection of signaling cascades converging on CREB (18,19). Genetically encoded indicators based on mutants of the green fluorescent protein (GFP) have become valuable tools to monitor spatiotemporal patterns of biochemical signals in live cells (20 -25). A number of indicators have ...

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“…10 and this study). Similarly, in cultured hippocampal neurons, immunoreactivities of ACI and ACVIII were found in various subcellular locations, in addition to plasma membranes (25,26). Transport of ACs therefore might be an important regulatory role for the AC family.…”

Section: Snapin Interaction With the N-terminal Domain Of Acvi-mentioning

confidence: 96%

Regulation of Type VI Adenylyl Cyclase by Snapin, a SNAP25-binding Protein

Chou

Huang

Lai

et al. 2004

Journal of Biological Chemistry

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In the present study, we used the N terminus (amino acids 1ϳ160) of type VI adenylyl cyclase (ACVI) as bait to screen a mouse brain cDNA library and identified Snapin as a novel ACVI-interacting molecule. Snapin is a binding protein of SNAP25, a component of the SNARE complex. Co-immunoprecipitation analyses confirmed the interaction between Snapin and full-length ACVI. Mutational analysis revealed that the interaction domains of ACVI and Snapin were located within amino acids 1ϳ86 of ACVI and 33-51 of Snapin, respectively. Co-localization of ACVI and Snapin was observed in primary hippocampal neurons. Moreover, expression of Snapin specifically eliminated protein kinase C (PKC)-mediated suppression of ACVI, but not that of cAMP-dependent protein kinase (PKA) or calcium. Mutation of the potential PKC and PKA phosphorylation sites of Snapin did not affect the ability of Snapin to reverse the PKC inhibitory effect on ACVI. Phosphorylation of Snapin by PKC or PKA therefore might not be crucial for Snapin action on ACVI. In contrast, Snapin ⌬33-51 , which harbors an internal deletion of amino acids 33-51 did not affect PKC-mediated inhibition of ACVI, supporting that amino acids 33-51 of Snapin comprises the ACVI-interacting region. Consistently, Snapin exerted no effect on PKC-mediated inhibition of an ACVI mutant (ACVI-⌬A87), which lacked the Snapin-interacting region (amino acids 1-86). Snapin thus reverses its action via direct interaction with the N terminus of ACVI. Collectively, we demonstrate herein that in addition to its association with the SNARE complex, Snapin also functions as a regulator of an important cAMP synthesis enzyme in the brain. Adenylyl cyclases (ACs)1 are a family of enzymes that produce cyclic AMP (cAMP) from ATP upon extracellular stimulation. To date, at least 9 membrane-bound ACs have been isolated and characterized (1). These enzymes are capable of integrating positive and negative signals that act directly through stimulation of G protein-coupled receptors (GPCRs) or indirectly via intracellular signaling molecules in isozyme-specific patterns. In addition, the regulatory properties and expression patterns of different AC isoforms greatly diverge and may account for the distinctive cell-and tissue-specific responsiveness of ACs. Recently, several different proteins, including RGS2 and the protein associated with Myc (PAM), have been shown to interact and modulate activity of different AC isozymes (2, 3), adding additional dimensions to the isozymespecific regulation of the AC superfamily.Except for the newly identified soluble AC, all membranebound AC members share a primary structure consisting of 12 transmembrane regions and 3 large cytoplasmic domains (N, C1a/b, and C2). The C1a and C2 domains, which form the catalytic core complex, are highly conserved and are homologous to each other. The N-terminal domains of ACs, in contrast, are variable among ACs, and have been demonstrated to play mostly regulatory roles (4, 5). Among the AC isozymes, ACVI is of particular interest, because...

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Synaptic concentration of type‐I adenylyl cyclase in cerebellar neurons

Cited by 14 publications

References 35 publications

Type 8 Adenylyl Cyclase Is Targeted to Excitatory Synapses and Required for Mossy Fiber Long-Term Potentiation

Type 8 Adenylyl Cyclase Is Targeted to Excitatory Synapses and Required for Mossy Fiber Long-Term Potentiation

Imaging CREB Activation in Living Cells

Regulation of Type VI Adenylyl Cyclase by Snapin, a SNAP25-binding Protein

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