Pde4

UniProt ID: Q9W4S9
Organism: Drosophila melanogaster
Review Status: COMPLETE
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Gene Description

Pde4 (dunce, dnc) encodes the Drosophila PDE4-class cAMP-specific 3',5'-cyclic phosphodiesterase, which hydrolyzes cAMP to AMP and so limits the amplitude and duration of cAMP/PKA signals. The locus produces many isoforms with different N-termini from alternative promoters and splicing; this entry (Q9W4S9) covers isoforms N and G, a 983-residue product that carries the PDE4 upstream conserved region and the complete metal-dependent catalytic domain shared by all dunce isoforms. The enzyme is concentrated in mushroom body neuropil, and loss of dunce activity raises cAMP, alters synaptic excitation, neuronal excitability and terminal arborization, and disrupts associative and nonassociative learning, short-term and anesthesia-resistant memory, circadian period, temperature preference and female post-mating behavior and fertility.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0001661 conditioned taste aversion
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Larval aversive odor-quinine conditioning fails in dnc1 mutants; a behavioral readout of cAMP-dependent plasticity.
Reason: In the cited larval paradigm an odorant is paired with quinine, which fits the GO definition (a chemical compound coupled with a noxious stimulus). dnc1 larvae fail to form this memory while their naive olfactory and quinine responses are normal, so the defect is in plasticity, not sensation. The gene product's own contribution is cAMP hydrolysis in the relevant neurons; the behavior is an organismal outcome and is kept as non-core.
Supporting Evidence:
PMID:19158309
we examined mutant larvae of rut 1 and dnc 1 , and found that both mutants failed to show significant RI decrement after aversive LIN/QH conditioning
GO:0001661 conditioned taste aversion
IMP
PMID:19158309
Distinctive neuronal networks and biochemical pathways for a...
KEEP AS NON CORE
Summary: Larval aversive odor-quinine conditioning fails in dnc1 mutants; a behavioral readout of cAMP-dependent plasticity.
Reason: In the cited larval paradigm an odorant is paired with quinine, which fits the GO definition (a chemical compound coupled with a noxious stimulus). dnc1 larvae fail to form this memory while their naive olfactory and quinine responses are normal, so the defect is in plasticity, not sensation. The gene product's own contribution is cAMP hydrolysis in the relevant neurons; the behavior is an organismal outcome and is kept as non-core.
Supporting Evidence:
PMID:19158309
we examined mutant larvae of rut 1 and dnc 1 , and found that both mutants failed to show significant RI decrement after aversive LIN/QH conditioning
GO:0004114 3',5'-cyclic-nucleotide phosphodiesterase activity
IEA
GO_REF:0000002
MODIFY
Summary: Correct but general; the dunce enzyme is cAMP-specific.
Reason: InterPro2GO assigns the generic cyclic-nucleotide PDE activity from the PDEase catalytic domain. Expression of dnc cDNA in yeast gave cAMP PDE activity matching the fly enzyme, Q9W4S9 carries the full catalytic domain with every annotated catalytic and cAMP/metal-binding residue of the canonical entry, and the PAINT IBD for GO:0004115 sits on an ancestral node (PTN001682918) that includes dnc. Refine to the cAMP-specific term the gene already carries.
Supporting Evidence:
PMID:1660926
Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
file:DROME/Pde4/Pde4-bioinformatics/RESULTS.md
All P12252 catalytic features map with identical residues
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
IEA
GO_REF:0000120
ACCEPT
Summary: Core activity: hydrolysis of cAMP to AMP.
Reason: The dnc locus encodes the cAMP-specific PDE whose activity is lost in dnc mutants; a dnc cDNA expressed in yeast produced cAMP PDE activity with the properties of the fly enzyme. Q9W4S9 (isoforms N/G) shares an identical 614-residue C-terminal block with the canonical dnc entry P12252, including the whole PDEase domain and all catalytic residues, so the locus-level biochemistry applies to this product. The ISS row's donor, yeast PDE2 (PTHR11347:SF198), is in a different PANTHER subfamily from dnc (SF219), but both descend from PAINT node PTN001682918, where cAMP PDE activity was placed by IBD, so the transfer is phylogenetically consistent.
Supporting Evidence:
PMID:1660926
Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
PMID:3030881
Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
file:DROME/Pde4/Pde4-bioinformatics/RESULTS.md
All P12252 catalytic features map with identical residues
GO:0004115 3',5'-cyclic-AMP phosphodiesterase activity
ISS
GO_REF:0000024
ACCEPT
Summary: Core activity: hydrolysis of cAMP to AMP.
Reason: The dnc locus encodes the cAMP-specific PDE whose activity is lost in dnc mutants; a dnc cDNA expressed in yeast produced cAMP PDE activity with the properties of the fly enzyme. Q9W4S9 (isoforms N/G) shares an identical 614-residue C-terminal block with the canonical dnc entry P12252, including the whole PDEase domain and all catalytic residues, so the locus-level biochemistry applies to this product. The ISS row's donor, yeast PDE2 (PTHR11347:SF198), is in a different PANTHER subfamily from dnc (SF219), but both descend from PAINT node PTN001682918, where cAMP PDE activity was placed by IBD, so the transfer is phylogenetically consistent.
Supporting Evidence:
PMID:1660926
Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
PMID:3030881
Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
file:DROME/Pde4/Pde4-bioinformatics/RESULTS.md
All P12252 catalytic features map with identical residues
GO:0006198 cAMP catabolic process
IEA
GO_REF:0000041
ACCEPT
Summary: The enzyme itself catalyzes the catabolic step (cAMP to AMP).
Reason: PDE4-class enzymes perform the single step of the cAMP degradation pathway (UniPathway UPA00762). dnc loss elevates cAMP levels and the amplitude of daily cAMP peaks in heads, consistent with this product executing cAMP catabolism.
Supporting Evidence:
PMID:1660926
Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
PMID:3030881
Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
PMID:7946340
dnc mutations increase the amplitude of daily cAMP peaks
GO:0007165 signal transduction
IEA
GO_REF:0000002
MODIFY
Summary: True but uninformative; the PDE dampens cAMP/PKA signaling.
Reason: The InterPro2GO mapping gives generic signal transduction. A cAMP PDE does not transmit a signal; it terminates the cAMP second-messenger signal. The informative process is negative regulation of cAMP/PKA signal transduction, which PAINT curators assign by IBA to all four human PDE4 paralogs and to other cAMP-hydrolysing PDE subfamilies. In dnc mutants cAMP rises, and in embryonic motoneurons the dunce background mimics elevated cAMP/PKA activity.
Supporting Evidence:
PMID:3030881
Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
PMID:14507965
Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase
PMID:7946340
dnc mutations increase the amplitude of daily cAMP peaks
GO:0007268 chemical synaptic transmission
IEA
GO_REF:0000117
MODIFY
Summary: dunce modulates synaptic transmission through cAMP; it does not carry out transmission.
Reason: Mutant analyses show that loss of dunce PDE activity raises synaptic excitation and changes neuronal excitability and Ca2+ dynamics through cAMP/PKA. The enzyme does none of the steps of transmitter release or reception; it regulates the strength of transmission by limiting cAMP. The cited 12040051 study is mainly about growth-cone Ca2+ regulation; the curator's reading is respected but the term is refined, not removed. Modulation of chemical synaptic transmission is the accurate process.
Supporting Evidence:
PMID:14507965
Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase
PMID:12040051
These mutations cause deficiencies in several learning paradigms and alter synaptic transmission, growth cone motility, and action potential generation.
GO:0007268 chemical synaptic transmission
IMP
PMID:12040051
Regional calcium regulation within cultured Drosophila neuro...
MODIFY
Summary: dunce modulates synaptic transmission through cAMP; it does not carry out transmission.
Reason: Mutant analyses show that loss of dunce PDE activity raises synaptic excitation and changes neuronal excitability and Ca2+ dynamics through cAMP/PKA. The enzyme does none of the steps of transmitter release or reception; it regulates the strength of transmission by limiting cAMP. The cited 12040051 study is mainly about growth-cone Ca2+ regulation; the curator's reading is respected but the term is refined, not removed. Modulation of chemical synaptic transmission is the accurate process.
Supporting Evidence:
PMID:14507965
Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase
PMID:12040051
These mutations cause deficiencies in several learning paradigms and alter synaptic transmission, growth cone motility, and action potential generation.
GO:0007268 chemical synaptic transmission
IMP
PMID:14507965
Postsynaptic protein kinase A reduces neuronal excitability ...
MODIFY
Summary: dunce modulates synaptic transmission through cAMP; it does not carry out transmission.
Reason: Mutant analyses show that loss of dunce PDE activity raises synaptic excitation and changes neuronal excitability and Ca2+ dynamics through cAMP/PKA. The enzyme does none of the steps of transmitter release or reception; it regulates the strength of transmission by limiting cAMP. The cited 12040051 study is mainly about growth-cone Ca2+ regulation; the curator's reading is respected but the term is refined, not removed. Modulation of chemical synaptic transmission is the accurate process.
Supporting Evidence:
PMID:14507965
Synaptic excitation is increased in genetic backgrounds that lack either a cAMP-specific phosphodiesterase
PMID:12040051
These mutations cause deficiencies in several learning paradigms and alter synaptic transmission, growth cone motility, and action potential generation.
GO:0007612 learning
IMP
PMID:16135747
Induction of cAMP response element-binding protein-dependent...
MODIFY
Summary: The supporting study assays larval appetitive olfactory learning; refine to olfactory learning.
Reason: PMID:16135747 shows dnc1 larvae fail odor-sucrose appetitive learning. The broad learning term is correct but the evidence supports the more specific olfactory learning term, which the gene already carries. This remains a non-core organismal phenotype downstream of cAMP hydrolysis.
Proposed replacements: olfactory learning
Supporting Evidence:
PMID:16135747
the requirement of both rut and dnc activities strongly argues for the importance of cAMP signaling for larval olfactory learning
IMP
PMID:10970024
Identification of Drosophila mutant with memory defects afte...
MODIFY
Summary: Memory phenotype of dnc is a short-term memory defect; refine to short-term memory.
Reason: The annotated study uses dnc as the reference short-term memory mutant in courtship conditioning, and the larval and adult conditioning studies show dnc loss affecting short-lived and anesthesia-resistant memory components. The broad memory term is correct but general; short-term memory and anesthesia-resistant memory are already carried. Non-core organismal outcome.
Proposed replacements: short-term memory
Supporting Evidence:
PMID:10970024
the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutants dnc and rut
PMID:19158309
we examined mutant larvae of rut 1 and dnc 1 , and found that both mutants failed to show significant RI decrement after aversive LIN/QH conditioning
GO:0007614 short-term memory
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: dnc mutants are classical short-term memory mutants.
Reason: dnc1 larvae fail to show short-term aversive memory; the defect reflects disrupted cAMP dynamics in memory circuits. Kept as non-core because the gene product's own role is cAMP hydrolysis.
Supporting Evidence:
PMID:19158309
we examined mutant larvae of rut 1 and dnc 1 , and found that both mutants failed to show significant RI decrement after aversive LIN/QH conditioning
PMID:10970024
the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutants dnc and rut
GO:0007614 short-term memory
IMP
PMID:19158309
Distinctive neuronal networks and biochemical pathways for a...
KEEP AS NON CORE
Summary: dnc mutants are classical short-term memory mutants.
Reason: dnc1 larvae fail to show short-term aversive memory; the defect reflects disrupted cAMP dynamics in memory circuits. Kept as non-core because the gene product's own role is cAMP hydrolysis.
Supporting Evidence:
PMID:19158309
we examined mutant larvae of rut 1 and dnc 1 , and found that both mutants failed to show significant RI decrement after aversive LIN/QH conditioning
PMID:10970024
the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutants dnc and rut
GO:0007615 anesthesia-resistant memory
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: dnc-sensitive cAMP signals in antennal-lobe local neurons and Kenyon cells support anesthesia-resistant memory.
Reason: Cell-type-specific manipulation localizes the dnc requirement for ARM. This is a well-supported circuit-level role of the enzyme but remains an organismal memory phenotype.
Supporting Evidence:
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
GO:0007615 anesthesia-resistant memory
IMP
PMID:23197709
Consolidated and labile odor memory are separately encoded w...
KEEP AS NON CORE
Summary: dnc-sensitive cAMP signals in antennal-lobe local neurons and Kenyon cells support anesthesia-resistant memory.
Reason: Cell-type-specific manipulation localizes the dnc requirement for ARM. This is a well-supported circuit-level role of the enzyme but remains an organismal memory phenotype.
Supporting Evidence:
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
GO:0007617 mating behavior
TAS
PMID:14504657
Sex-peptides: seminal peptides of the Drosophila male.
KEEP AS NON CORE
Summary: dunce null females remate unusually often.
Reason: The TAS review cannot be read here, but primary data show dunce null females mate every 22-24 h, a defect in post-mating behavioral change attributed to uncontrolled cAMP after mating. The term is accurate as an organismal phenotype; non-core.
Supporting Evidence:
PMID:3030881
Mutant dunce females, mate every 22-24 hr.
PMID:3030881
Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
GO:0007619 courtship behavior
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Courtship alteration in dnc males is experience-dependent (conditioned courtship).
Reason: Naive dnc males court and mate normally; the defect appears only after experience, as a failure of courtship conditioning. The term is not wrong, since experienced dnc males court differently, but it reflects the learning defect rather than a role in generating courtship. Kept as non-core; the learning terms capture the defect more precisely.
Supporting Evidence:
PMID:3934032
In this situation, dnc+ males spent much less time in courtship with immature males and achieved copulation in one-third the time required for dncM14 males.
PMID:3934032
dnc+ and dncM14 males were indistinguishable in their response and mating efficiency when individually paired with virgin females
GO:0007619 courtship behavior
TAS
PMID:11092827
Courtship in Drosophila.
KEEP AS NON CORE
Summary: Courtship alteration in dnc males is experience-dependent (conditioned courtship).
Reason: Naive dnc males court and mate normally; the defect appears only after experience, as a failure of courtship conditioning. The term is not wrong, since experienced dnc males court differently, but it reflects the learning defect rather than a role in generating courtship. Kept as non-core; the learning terms capture the defect more precisely.
Supporting Evidence:
PMID:3934032
In this situation, dnc+ males spent much less time in courtship with immature males and achieved copulation in one-third the time required for dncM14 males.
PMID:3934032
dnc+ and dncM14 males were indistinguishable in their response and mating efficiency when individually paired with virgin females
GO:0007619 courtship behavior
TAS
PMID:11715043
Drosophila: genetics meets behaviour.
KEEP AS NON CORE
Summary: Courtship alteration in dnc males is experience-dependent (conditioned courtship).
Reason: Naive dnc males court and mate normally; the defect appears only after experience, as a failure of courtship conditioning. The term is not wrong, since experienced dnc males court differently, but it reflects the learning defect rather than a role in generating courtship. Kept as non-core; the learning terms capture the defect more precisely.
Supporting Evidence:
PMID:3934032
In this situation, dnc+ males spent much less time in courtship with immature males and achieved copulation in one-third the time required for dncM14 males.
PMID:3934032
dnc+ and dncM14 males were indistinguishable in their response and mating efficiency when individually paired with virgin females
GO:0007619 courtship behavior
TAS
PMID:12486700
Genetic basis of male sexual behavior.
KEEP AS NON CORE
Summary: Courtship alteration in dnc males is experience-dependent (conditioned courtship).
Reason: Naive dnc males court and mate normally; the defect appears only after experience, as a failure of courtship conditioning. The term is not wrong, since experienced dnc males court differently, but it reflects the learning defect rather than a role in generating courtship. Kept as non-core; the learning terms capture the defect more precisely.
Supporting Evidence:
PMID:3934032
In this situation, dnc+ males spent much less time in courtship with immature males and achieved copulation in one-third the time required for dncM14 males.
PMID:3934032
dnc+ and dncM14 males were indistinguishable in their response and mating efficiency when individually paired with virgin females
GO:0007623 circadian rhythm
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: dnc mutants show shortened free-running period and enhanced light-induced phase delays.
Reason: Primary data show altered circadian pacemaker function and higher-amplitude daily cAMP peaks in dnc mutants. The PDE shapes cAMP signals that feed into the clock and its resetting; this is a modulatory, non-core role.
Supporting Evidence:
PMID:7946340
dnc mutants exhibit augmented light-induced phase delays and shortened circadian periods, which indicate altered pacemaker function.
PMID:7946340
dnc mutations increase the amplitude of daily cAMP peaks
GO:0007623 circadian rhythm
TAS
PMID:12486701
Genetic analysis of the circadian system in Drosophila melan...
KEEP AS NON CORE
Summary: dnc mutants show shortened free-running period and enhanced light-induced phase delays.
Reason: Primary data show altered circadian pacemaker function and higher-amplitude daily cAMP peaks in dnc mutants. The PDE shapes cAMP signals that feed into the clock and its resetting; this is a modulatory, non-core role.
Supporting Evidence:
PMID:7946340
dnc mutants exhibit augmented light-induced phase delays and shortened circadian periods, which indicate altered pacemaker function.
PMID:7946340
dnc mutations increase the amplitude of daily cAMP peaks
GO:0008081 phosphoric diester hydrolase activity
IEA
GO_REF:0000002
MODIFY
Summary: Too general; the specific activity is cAMP phosphodiesterase.
Reason: The phosphoric diester hydrolase parent is entailed by the cAMP PDE activity supported biochemically and by full conservation of the catalytic site in this product.
Supporting Evidence:
PMID:1660926
Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
file:DROME/Pde4/Pde4-bioinformatics/RESULTS.md
All P12252 catalytic features map with identical residues
GO:0008306 associative learning
IMP
PMID:10970024
Identification of Drosophila mutant with memory defects afte...
KEEP AS NON CORE
Summary: dnc males fail courtship conditioning, an associative paradigm.
Reason: The annotated study treats dnc as a known short-term memory mutant in conditioned courtship suppression, and olfactory conditioning studies confirm associative defects. Associative learning is as precise as this paradigm allows; non-core organismal phenotype.
Supporting Evidence:
PMID:10970024
the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutants dnc and rut
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
GO:0008355 olfactory learning
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Olfactory learning requires dnc in larvae and adults.
Reason: dnc1 larvae show no appetitive olfactory learning, and dnc-sensitive cAMP signals in antennal lobe and mushroom body neurons support olfactory memory. dunce PDE is concentrated in mushroom body neuropil. Well established, but downstream of the enzymatic role.
Supporting Evidence:
PMID:16135747
the requirement of both rut and dnc activities strongly argues for the importance of cAMP signaling for larval olfactory learning
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
PMID:1848082
Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil
GO:0008355 olfactory learning
TAS
PMID:11462211
Molecular biology and anatomy of Drosophila olfactory associ...
KEEP AS NON CORE
Summary: Olfactory learning requires dnc in larvae and adults.
Reason: dnc1 larvae show no appetitive olfactory learning, and dnc-sensitive cAMP signals in antennal lobe and mushroom body neurons support olfactory memory. dunce PDE is concentrated in mushroom body neuropil. Well established, but downstream of the enzymatic role.
Supporting Evidence:
PMID:16135747
the requirement of both rut and dnc activities strongly argues for the importance of cAMP signaling for larval olfactory learning
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
PMID:1848082
Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil
GO:0008355 olfactory learning
TAS
PMID:11715043
Drosophila: genetics meets behaviour.
KEEP AS NON CORE
Summary: Olfactory learning requires dnc in larvae and adults.
Reason: dnc1 larvae show no appetitive olfactory learning, and dnc-sensitive cAMP signals in antennal lobe and mushroom body neurons support olfactory memory. dunce PDE is concentrated in mushroom body neuropil. Well established, but downstream of the enzymatic role.
Supporting Evidence:
PMID:16135747
the requirement of both rut and dnc activities strongly argues for the importance of cAMP signaling for larval olfactory learning
PMID:23197709
dnc-sensitive cAMP signals support ARM within antennal lobe local neurons (LNs) and KCs.
PMID:1848082
Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil
GO:0040040 thermosensory behavior
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Temperature preference depends on cAMP/PKA levels in mushroom bodies.
Reason: The cited screen shows preferred temperature varies with cAMP and PKA activity in mushroom bodies across PKA-pathway mutants. Kept as a non-core behavioral outcome; dunce is not a thermosensor.
Supporting Evidence:
PMID:18594510
Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants.
GO:0040040 thermosensory behavior
IMP
PMID:18594510
cAMP signalling in mushroom bodies modulates temperature pre...
KEEP AS NON CORE
Summary: Temperature preference depends on cAMP/PKA levels in mushroom bodies.
Reason: The cited screen shows preferred temperature varies with cAMP and PKA activity in mushroom bodies across PKA-pathway mutants. Kept as a non-core behavioral outcome; dunce is not a thermosensor.
Supporting Evidence:
PMID:18594510
Preferred temperatures were affected by the level of cAMP and PKA activity in the MBs in various PKA pathway mutants.
GO:0045202 synapse
IEA
GO_REF:0000108
KEEP AS NON CORE
Summary: Plausible neuronal location; derived by inference from the synaptic-transmission process annotation.
Reason: The row is a GO_REF:0000108 inference from the chemical synaptic transmission annotation, not a localization assay. Immunostaining shows dunce PDE concentrated in mushroom body neuropil, a synapse-dense region, which is compatible with but does not show synaptic localization. Retained as non-core; no more specific location is supported.
Supporting Evidence:
PMID:1848082
Antibodies to the dnc PDE showed that the most intensely stained regions in the adult brain were the mushroom body neuropil
GO:0046958 nonassociative learning
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: dunce mutants show reduced habituation and short-lived sensitization.
Reason: Primary data show that the proboscis-extension reflex of dunce flies habituates less than normal and sensitization wanes rapidly, supporting the nonassociative learning annotation as a non-core organismal phenotype.
Supporting Evidence:
PMID:6808513
The dunce, turnip, and rutabaga mutants all habituate less than normal flies.
GO:0046958 nonassociative learning
TAS
PMID:14504657
Sex-peptides: seminal peptides of the Drosophila male.
KEEP AS NON CORE
Summary: dunce mutants show reduced habituation and short-lived sensitization.
Reason: Primary data show that the proboscis-extension reflex of dunce flies habituates less than normal and sensitization wanes rapidly, supporting the nonassociative learning annotation as a non-core organismal phenotype.
Supporting Evidence:
PMID:6808513
The dunce, turnip, and rutabaga mutants all habituate less than normal flies.
GO:0048675 axon extension
IEA
GO_REF:0000117
KEEP AS NON CORE
Summary: Elevated cAMP in dunce mutants enhances motor-terminal arborization.
Reason: The phenotype is excess arborization of larval NMJ terminals, so dunce limits growth via cAMP rather than taking part in axon extension. The IMP row is kept as non-core; a more accurate term would be a negative-regulation term for terminal growth, but the study is abstract-only here and the annotation is not rewritten from incomplete evidence.
Supporting Evidence:
PMID:14960616
Elevated cAMP levels in dunce mutants with reduced phosphodiesterase activity also cause enhanced arborization.
GO:0048675 axon extension
IMP
PMID:14960616
Neuronal activity and adenylyl cyclase in environment-depend...
KEEP AS NON CORE
Summary: Elevated cAMP in dunce mutants enhances motor-terminal arborization.
Reason: The phenotype is excess arborization of larval NMJ terminals, so dunce limits growth via cAMP rather than taking part in axon extension. The IMP row is kept as non-core; a more accurate term would be a negative-regulation term for terminal growth, but the study is abstract-only here and the annotation is not rewritten from incomplete evidence.
Supporting Evidence:
PMID:14960616
Elevated cAMP levels in dunce mutants with reduced phosphodiesterase activity also cause enhanced arborization.

Core Functions

Hydrolyzes cAMP to AMP with its metal-dependent PDE4 catalytic domain, terminating cAMP/PKA signals in neurons including mushroom body and antennal-lobe neurons, where this regulates synaptic excitation and memory.

Supporting Evidence:
  • PMID:1660926
    Expression of a cDNA clone in yeast containing a large portion of the open reading frame produced cAMP PDEase activity identical in properties to the Drosophila enzyme affected by the dnc mutation.
  • PMID:3030881
    Mutations of dunce alter or abolish the activity of this enzyme, produce elevated cAMP levels
  • file:DROME/Pde4/Pde4-bioinformatics/RESULTS.md
    All P12252 catalytic features map with identical residues
  • PMID:7946340
    dnc mutations increase the amplitude of daily cAMP peaks

References

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Suggested Questions for Experts

Q: Do isoforms N/G (Q9W4S9), which use a distinct N-terminal exon, differ from other dunce isoforms in expression pattern or subcellular targeting, for example in mushroom body or antennal-lobe neurons?

Q: The PAINT-derived IBA for cGMP phosphodiesterase activity (GO:0047555) on the dnc entry Q9W4T4 conflicts with the cAMP specificity of PDE4-class enzymes; should that node assignment be revisited?

Suggested Experiments

Experiment: Isoform-specific rescue of dnc null mutants with the N/G coding sequence, assaying head cAMP levels, anesthesia-resistant memory and female fertility, to test whether this N-terminal variant supports the locus functions.

Deep Research

Falcon

(Pde4-deep-research-falcon.md)

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FlyBase

(Pde4-deep-research-flybase.md)
FlyBase gene description for Pde4 (DROME) FlyBase

FlyBase gene description for Pde4 (DROME)

Phosphodiesterase 4 (Pde4) encodes a cAMP-specific phosphodiesterase, responsible for cAMP degradation. Pde4 product plays a pivotal role in neurological and behavioral plasticity including synaptic development and function, learning and courtship. The product of Pde4 is also known to affect regulation of several developmental processes such as oogenesis.

πŸ“š Additional Documentation

Notes

(Pde4-notes.md)

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Bioinformatics Results

(RESULTS.md)

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πŸ“„ View Raw YAML

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