Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Conti, Alana C.; Maas, James W.; Muglia, Lisa M.; Dave, Bhumy A.; Vogt, Sherri K.; Tran, Timothy T.; Rayhel, E. J.; Muglia, Louis J.

doi:10.1016/j.neuroscience.2007.01.045

Cited by 77 publications

(84 citation statements)

References 34 publications

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“…These compartmentalized effects of AC8 and AC1 also fit with recent evaluations of the subcellular localization of AC1 and AC8 protein. Although the domains are somewhat overlapping, AC1 and AC8 localize to primarily postsynaptic and presynaptic compartments, respectively (Conti et al, 2007).…”

Section: Camp and Presynaptic Potentiationmentioning

confidence: 99%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

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Glutamate generates fast postsynaptic depolarization throughout the CNS. The positive-feedback nature of glutamate signaling likely necessitates flexible adaptive mechanisms that help prevent runaway excitation. We have previously explored presynaptic adaptive silencing, a form of synaptic plasticity produced by ongoing neuronal activity and by strong depolarization. Unsilencing mechanisms that maintain active synapses and restore normal function after adaptation are also important, but mechanisms underlying such presynaptic reactivation remain unexplored. Here we investigate the involvement of the cAMP pathway in the basal balance between silenced and active synapses, as well as the recovery of baseline function after depolarization-induced presynaptic silencing. Activation of the cAMP pathway activates synapses that are silent at rest, and pharmacological inhibition of cAMP signaling silences basally active synapses. Adenylyl cyclase (AC) 1 and AC8, the major Ca 2ϩ -sensitive AC isoforms, are not crucial for the baseline balance between silent and active synapses. In cells from mice doubly deficient in AC1 and AC8, the baseline percentage of active synapses was only modestly reduced compared with wild-type synapses, and forskolin unsilencing was similar in the two genotypes. Nevertheless, after strong presynaptic silencing, recovery of normal function was strongly inhibited in AC1/AC8-deficient synapses. The entire recovery phenotype of the double null was reproduced in AC8-deficient but not AC1-deficient cells. We conclude that, under normal conditions, redundant cyclase activity maintains the balance between presynaptically silent and active synapses, but AC8 plays a particularly important role in rapidly resetting the balance of active to silent synapses after adaptation to strong activity.

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Section: Camp and Presynaptic Potentiationmentioning

confidence: 99%

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Moulder¹,

Jiang²,

Chang³

et al. 2008

J. Neurosci.

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“…Compared with AC1, whose activity is regulated by both G-proteins and Ca, AC8 is a pure Ca sensor. Recently, we found that the endogenous AC1 is preferentially localized in the postsynaptic density, whereas AC8 is detected mainly in the presynaptic active zone (Conti et al, 2007) (Fig. 7).…”

Section: Discussionmentioning

confidence: 90%

“…Moreover, we found that the endogenous AC1 was mainly localized at the postsynaptic density (PSD). The endogenous AC8 was preferentially concentrated at the presynaptic active zone (PAZ) (Conti et al, 2007). These findings suggest that AC1 and AC8 may play distinct roles in regulating activity-dependent plasticity.…”

Section: Introductionmentioning

confidence: 88%

“…After homogenization, the synaptosomes were isolated by sucrose gradient centrifugation (100,000 ϫ g for 1.5 h) as described previously (Phillips et al, 2001;Conti et al, 2007). The purified synaptosomes were further separated into extrasynaptic, PSD, and PAZ fractions as described previously (Conti et al, 2007) and subjected to 4 -12% SDS-PAGE. AC1 and AC8 were detected by Western blot analysis with the ECL methods (SuperSignal WestDura; Pierce, Rockford, IL).…”

Section: Methodsmentioning

confidence: 99%

“…7 A, B), they appeared to be highly specific for AC1 and AC8. The specific immunosignal was lost in AC1 KO mice when AC1 antibody was used (Conti et al, 2007) (Fig. 7A).…”

Section: The Function Of Ac8 In Working/episodic-like Memory During Tmentioning

confidence: 99%

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Ca-Stimulated Type 8 Adenylyl Cyclase Is Required for Rapid Acquisition of Novel Spatial Information and for Working/Episodic-Like Memory

Zhang¹,

Moon²,

Chan³

et al. 2008

J. Neurosci.

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Ca-stimulated adenylyl cyclases (ACs) transduce neuronal stimulation-evoked increase in calcium to the production of cAMP, which impinges on the regulation of many aspects of neuronal function. Type 1 and type 8 AC (AC1 and AC8) are the only ACs that are directly stimulated by Ca. Although AC1 function was implicated in regulating reference spatial memory, the function of AC8 in memory formation is not known. Because of the different biochemical properties of AC1 and AC8, these two enzymes may have distinct functions. For example, AC1 activity is regulated by both Ca and G-proteins. In contrast, AC8 is a pure Ca sensor. It is neither stimulated by G s nor inhibited by G i . Recent studies also suggested that AC1 and AC8 were differentially concentrated at different subcellular domains, implicating that Ca-stimulated signaling might be compartmentalized. In this study, we used AC8 knock-out (KO) mice and found behavioral deficits in memory retention for temporal dissociative passive avoidance and object recognition memory. When examined by Morris water maze, AC8 KO mice showed normal reference memory. However, the acquisition of newer spatial information was defective in AC8 KO mice. Furthermore, AC8 KO mice were severely impaired in hippocampus-dependent episodic-like memory when examined by the delayed matching-to-place task. Because AC8 is preferentially localized at the presynaptic active zone, our results suggest a novel role of presynaptic cAMP signaling in memory acquisition and retention, as well as distinct mechanisms underlying reference and working/episodic-like memory.

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Aspects of astrocytic cAMP signaling with an emphasis on the putative power of compartmentalized signals in health and disease

Reuschlein

Jakobsen

Mertz

et al. 2019

Glia

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This review discusses aspects of known and putative compartmentalized 3′,5′‐cyclic adenosine monophosphate (cAMP) signaling in astrocytes, a cell type that has turned out to be a key player in brain physiology and pathology. cAMP has attracted less attention than Ca2+ in recent years, but could turn out to rival Ca2+ in its potential to drive cellular functions and responses to intra— and extracellular cues. Further, Ca2+ and cAMP are known to engage in extensive crosstalk and cAMP signals often take place within subcellular compartments revolving around multi‐protein signaling complexes; however, we know surprisingly little about this in astrocytes. Here, we review aspects of astrocytic cAMP signaling, provide arguments for an increased interest in this subject, suggest possible future research directions within the field, and discuss putative drug targets.

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Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Cited by 77 publications

References 34 publications

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Ca-Stimulated Type 8 Adenylyl Cyclase Is Required for Rapid Acquisition of Novel Spatial Information and for Working/Episodic-Like Memory

Aspects of astrocytic cAMP signaling with an emphasis on the putative power of compartmentalized signals in health and disease

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Distinct regional and subcellular localization of adenylyl cyclases type 1 and 8 in mouse brain

Cited by 77 publications

References 34 publications

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca2+-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

Ca-Stimulated Type 8 Adenylyl Cyclase Is Required for Rapid Acquisition of Novel Spatial Information and for Working/Episodic-Like Memory

Aspects of astrocytic cAMP signaling with an emphasis on the putative power of compartmentalized signals in health and disease

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A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing

A Specific Role for Ca²⁺-Dependent Adenylyl Cyclases in Recovery from Adaptive Presynaptic Silencing