A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1): Dopamine metabolism

Zilberman-Peled, Bina; Ron, Benny; Gross, Aviva; Finberg, J. P. M.; Gothilf, Yoav

doi:10.1016/j.brainres.2005.12.028

Cited by 34 publications

(45 citation statements)

References 62 publications

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“…Candidate functions/roles include neurotransmission, which is consistent with the finding that AANAT acetylates dopamine, a retinal transmitter (21); acetylation of dopamine might also lead to a novel messenger. Another possible role is detoxification (supplemental Fig.…”

Section: Role Of Retinal Aanatsupporting

confidence: 61%

Arylalkylamine N-Acetyltransferase: “the Timezyme”

Klein

2007

Journal of Biological Chemistry

374

347

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Arylalkylamine N-acetyltransferase controls daily changes in melatonin production by the pineal gland and thereby plays a unique role in biological timing in vertebrates. Arylalkylamine N-acetyltransferase is also expressed in the retina, where it may play other roles in addition to signaling, including neurotransmission and detoxification. Large changes in activity reflect cyclic 3,5-adenosine monophosphate-dependent phosphorylation of arylalkylamine N-acetyltransferase, leading to formation of a regulatory complex with 14-3-3 proteins. This activates the enzyme and prevents proteosomal proteolysis. The conserved features of regulatory systems that control arylalkylamine N-acetyltransferase are a circadian clock and environmental lighting.Arylalkylamine N-acetyltransferase (AANAT; EC 2.1.3.87) 2 plays a unique role in vertebrate biology by controlling the rhythmic production of melatonin in the pineal gland ( Fig. 1) (1). Activity increases 10-to 100-fold at night, causing an increase in the production and release of melatonin. The dynamics of AANAT activity are remarkable: the doubling time is ϳ15 min at night, and the halving time of the decrease that follows a night 3 light transition is ϳ3.5 min (2, 3). Circulating melatonin levels parallel changes in synthesis and release, due to rapid clearance by the liver (1).The rhythmic pattern of activity in the melatonin pathway is a conserved feature of vertebrate biology, consistent with the role of melatonin as the vertebrate hormone of time, i.e. high levels signal night and low levels signal day. Although this signaling pattern is conserved, it is used in a variety of species-dependent ways to optimally control seasonal and daily changes in physiology (1). The unique role that AANAT plays in vertebrate time keeping justifies the title of "the Timezyme." Our knowledge of the biological chemistry of AANAT is summarized in this overarching review. Aanat Genes and EvolutionThe AANAT Family-Aanat and Aanat homologs form the AANAT family, which is part of the large Gcn5-related acetyltransferase (GNAT) superfamily (4, 5). All GNAT family members share common structural features associated with acetyl coenzyme A (AcCoA) binding; in addition, each member family has unique features reflecting substrate specificity for each of a wide range of substrates (e.g. aminoglycosides, diamines, puromycin, histones, and arylalkylamines). The GNAT superfamily also includes another arylalkylamine N-acetyltransferase family, represented by dopamine N-aceyltransferase (Dat), which is expressed in Drosophila melanogaster (6). Dat is not involved time keeping; rather, it functions in cuticle sclerotization and neurotransmission (6). DAT and AANAT family members have not been found in the same genome.AANAT family members have only been found in Grampositive bacteria, fungi, algae, cephalochordates, and vertebrates; family members are not found in higher plants, insects, nematodes, or urochordates (7). This distribution may be explained by the initial appearance of the ancestral Aanat in ...

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Section: Role Of Retinal Aanatsupporting

confidence: 61%

Arylalkylamine N-Acetyltransferase: “the Timezyme”

Klein

2007

Journal of Biological Chemistry

374

347

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“…AANAT-1, in contrast, would appear to function to acetylate a range of arylalkylamines in the retina, either for detoxification, biosynthesis of other compounds, or modulation of the amount of an active form of a compound. For example, dopamine is acetylated by AANAT-1a in seabream retina (Zilberman-Peled et al, 2006). Thus, the existence of multiple AANATs in fish supports the view that the ancestral photoreceptor evolved into the retinal photoreceptor and pinealocyte because of different evolutionary pressures , with melatonin synthesis being selected for in the pineal gland and another function in the retinal photoreceptors.…”

Section: A Third Aanat Gene In Percomorph Fishesmentioning

confidence: 61%

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Coon

Klein

2006

Molecular and Cellular Endocrinology

106

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The melatonin rhythm-generating enzyme, arylalkylamine N-acetyltransferase (AANAT) is known to have recognizable ancient homologs in bacteria and fungi, but not in other eukaryotes. Analysis of new cDNA and genomic sequences has identified several additional homologs in other groupings. First, an AANAT homolog has been found in the genome of the cephalochordate amphioxus, representing the oldest homolog in chordates. Second, two AANAT homologs have been identified in unicellular green algae. The homologs in amphioxus, unicellular green algae, fungi and bacteria are similarly primitive in that they lack sequences found in vertebrate AANATs that are involved in regulation and that facilitate binding and catalysis. In addition, all these sequences are intronless. These features are consistent with horizontal transfer of the AANAT ancestor from bacteria to green algae, fungi and chordates. Lastly, a third AANAT gene has been found in teleost fish, suggesting that AANAT genes serve multiple functions in addition to melatonin synthesis.

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“…This may be the case with fish aanat; the ancestral gene might have been expressed in all photoreceptor cells, as seen in chickens and mammals, while subsequent mutations in the duplicated genes subdivided their function and profile of expression to the pineal gland (aanat2) and retina (aanat1), as seen in trout, pike and seabream , Benyassi et al 2000, Zilberman-Peled et al 2004. Since in zebrafish both aanat genes are co-expressed in the retina, it is likely that they are required for different retinal functions (Zilberman-Peled et al 2006). This possibility is reflected in their differential tissue distribution and in their differential regulation by the circadian clock and light in the retina (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…However, in several fish species retinal melatonin levels were found to be high during the day (Falcon et al 2003, Zilberman-Peled et al 2006. In frog retina, a poor correlation between aanat activity and melatonin Figure 6 Co-operative activation by BMAL/CLOCK heterodimer and OTX5 via aanat1 and aanat2 promoters.…”

Section: Discussionmentioning

confidence: 99%

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Zebrafish arylalkylamine-N-acetyltransferase genes – targets for regulation of the circadian clock

Appelbaum

Vallone²,

Anzulovich³

et al. 2006

Journal of Molecular Endocrinology

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Daily rhythms of melatonin production are controlled by changes in the activity of arylalkylamine-N-acetyltransferase (AANAT). Zebrafish possess two aanats, aanat1 and aanat2; the former is expressed only in the retina and the latter is expressed in both the retina and the pineal gland. Here, their differential expression and regulation were studied using transcript quantification and transient and stable in vivo and in vitro transfection assays. In the pineal gland, the aanat2 promoter exhibited circadian clock-controlled activity, as indicated by circadian rhythms of Enhanced green fluorescent protein (EGFP) mRNA in AANAT2:EGFP transgenic fish. In vivo transient expression analyses of the aanat2 promoter indicated that E-box and photoreceptor conserved elements (PCE) are required for expression in the pineal gland. In the retina, the expression of both genes was characterized by a robust circadian rhythm of their transcript levels. In constant darkness, the rhythmic expression of retinal aanat2 persisted while the aanat1 rhythm disappeared; indicating that the former is controlled by a circadian clock and the latter is also light driven. In the light-entrainable clock-containing PAC-2 zebrafish cell line, both stably transfected aanat1 and aanat2 promoters exhibited a clock-controlled circadian rhythm, characteristic for an E-box-driven expression. Transient co-transfection experiments in NIH-3T3 cells revealed that the two, E-box-and PCE-containing, promoters are driven by the synergistic action of BMAL/CLOCK and orthehodenticle homeobox 5. This study has revealed a shared mechanism for the regulation of two related genes, yet describes their differential phases and photic responses which may be driven by other gene-specific regulatory mechanisms and tissue-specific transcription factor profiles.

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A possible new role for fish retinal serotonin-N-acetyltransferase-1 (AANAT1): Dopamine metabolism

Cited by 34 publications

References 62 publications

Arylalkylamine N-Acetyltransferase: “the Timezyme”

Arylalkylamine N-Acetyltransferase: “the Timezyme”

Evolution of arylalkylamine N-acetyltransferase: Emergence and divergence

Zebrafish arylalkylamine-N-acetyltransferase genes – targets for regulation of the circadian clock

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