Melatonin pathway: breaking the ‘high-at-night’ rule in trout retina

Melatonin (N-acetyl-5-methoxytrypamine) is the vertebrate hormone of the night: circulating levels at night are markedly higher than day levels. This increase is driven by precisely regulated increases in acetylation of serotonin in the pineal gland by arylalkylamine N-acetyltransferase (AANAT), the penultimate enzyme in the synthesis of melatonin. This unique essential role of AANAT in vertebrate timekeeping is recognized by the moniker the timezyme. AANAT is also found in the retina, where melatonin is thought to play a paracrine role. Here, we focused on the evolution of AANAT in early vertebrates. AANATs from Agnathans (lamprey) and Chondrichthyes (catshark and elephant shark) were cloned, and it was found that pineal glands and retinas from these groups express a form of AANAT that is compositionally, biochemically, and kinetically similar to AANATs found in bony vertebrates (VT-AANAT). Examination of the available genomes indicates that VT-AANAT is absent from other forms of life, including the Cephalochordate amphioxus. Phylogenetic analysis and evolutionary rate estimation indicate that VT-AANAT evolved from the nonvertebrate form of AANAT after the Cephalochordate-Vertebrate split over one-half billion years ago. The emergence of VT-AANAT apparently involved a dramatic acceleration of evolution that accompanied neofunctionalization after a duplication of the nonvertebrate AANAT gene. This scenario is consistent with the hypotheses that the advent of VT-AANAT contributed to the evolution of the pineal gland and lateral eyes from a common ancestral photodetector and that it was not a posthoc recruitment.E yes have evolved in all animals to facilitate interactions with the photic environment (1, 2). However, among animals, vertebrates are unique in that they also possess a photoneuroendocrine structure, the pineal gland (3). It converts the 24-h rhythm in environmental lighting into a 24-h rhythm in circulating melatonin, thereby providing a unique and valuable signal of the photic environment. The details of pineal evolution are not clear (4, 5). However, it has been posited that an essential element was arylalkylamine N-acetyltransferase (AANAT; E.C. 2.3.1.87), the penultimate enzyme in the melatonin biosynthesis pathway (6-8); this scenario is referred to as the AANAT hypothesis of pineal evolution (7,8).AANAT catalyzes the N-acetylation of arylalkylamines using acetyl CoA (AcCoA) as the acetyl group donor. The AANAT family, which belongs to the GCN5 superfamily (9, 10), is composed of two subfamilies termed vertebrate (VT) AANAT and nonvertebrate (NV) AANAT. † This nomenclature reflects the phylogenetic distribution of the family members (13-17). The most striking differences between VT-and NV-AANAT are found in regulatory and catalytic regions of the encoded proteins (Fig. 1), consistent with different metabolic roles (7,8).The NV-AANAT is thought to perform a detoxification function through acetylation of a broad range of endogenous and exogenous arylalkylamines and polyamines (13-16). It has been fo...

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“…2A) (see above). Midday/midnight differences are consistent with previous observations made in bony fish and tetrapods (6,8,32).…”

Section: Resultssupporting

confidence: 82%

“…3I). The labeling in the lamprey and catshark retina resembles the pattern seen in the teleost retina (32). Native enzyme activity.…”

Section: Resultsmentioning

confidence: 95%

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Falcón

Coon

Besseau

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…As previously shown in several other species of vertebrates including some teleosts such as European sea bass (Iigo et al, 1997;Bayarri et al, 2002), rainbow trout, Oncorhynchus mykiss (Besseau et al, 2006) and Nile tilapia (Iigo et al, 2007), retinal melatonin rhythm in the present study was phase shifted (4 fold higher during the day than during the night) in comparison to the plasma rhythm. This would suggest that retinal melatonin in Nile tilapia is most likely having a different role than melatonin produced by the pineal gland and would not significantly contribute to night-time plasma melatonin levels.…”

Section: Discussionsupporting

confidence: 83%

“…In rainbow trout, at least two different melatonin synthesis pathways appear to exist due to the presence of different precursor subtypes differentially expressed in the pineal (AANAT2) and the retina (AANAT1) (Falcon et al, 2003;Besseau et al, 2006). The recent discovery of more than one AANAT1 subtype (AANAT1a and b) in two species of puffer fish and medaka further complicates the picture in teleosts and also suggests multiple roles for these genes other than melatonin synthesis .…”

Section: Discussionmentioning

confidence: 99%

“…In a number of teleost species, rhythmic melatonin production by both tissues is in phase (low during day and high at night) while in some other vertebrates (including teleosts), melatonin production in retina can be reversed thus being higher during the day than at night (Gern et al, 1978;Yu et al, 1981;Reiter et al, 1983;Serino et al, 1993;Iigo et al, 1997;Besseau et al, 2006;Iigo et al, 2007b). These phase shift patterns of secretion could be linked to differences within the melatonin biosynthesis pathway leading to the production of melatonin and more specifically arylalkylamine N-acetyltransferase (AANAT) which is the enzyme found in all vertebrates involved in the conversion of serotonin into melatonin (Klein et al, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Retinal light input is required to sustain plasma melatonin rhythms in Nile tilapia Oreochromis niloticus niloticus

Martinez-Chavez

Migaud

2009

Brain Research

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The aim of this work was to confirm previous findings suggesting that the eyes are required for night-time melatonin production in Nile tilapia and further characterise this divergent circadian organisation. To do so, melatonin levels were firstly measured in eyecups and plasma to determine circadian patterns of melatonin production.Secondly, the effect of partial ophthalmectomy on the suppression of melatonin production was determined in vivo as well as ex vivo pineal light/dark sensitivity.Finally, to investigate whether such findings could be related to post-surgery stress, melatonin analyses were performed in the subsequent 24 h and 7 days postophthalmectomy with cortisol levels assessed as an indicator of stress. Our results showed an inverse pattern of melatonin production in the eye cups of tilapia compared to blood circulating levels, suggesting different roles played by melatonin in these two tissues. Results then demonstrated that total or partial ophthalmectomy resulted in the suppression of night-time melatonin production. Furthermore, although pineals in culture were shown to be photosensitive, night-time melatonin levels were much lower than seen in other species. Finally, when performing sampling immediately or one week post-surgery, no difference in the melatonin profiles were observed. It is therefore unlikely that post-surgery stress would explain such suppression in melatonin production although all fish displayed high cortisol levels most probably due to social and handling stress. Taken together, these results provide further evidence of a new type of circadian organisation in a teleost species where the eyes are required to sustain night time melatonin levels. Section: Regulatory systems

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Daily and Seasonal Expression Profile of Serum Melatonin and Its Biosynthesizing Enzyme Genes (tph1, aanat1, aanat2, andhiomt) in Pineal Organ and Retina: A Study under Natural Environmental Conditions in a Tropical Carp,Catla catla

et al. 2016

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The tropical carp Catla catla is gaining importance for the studies of the impact of environmental changes on aquatic animals due to its surface dwelling habitat. To date, no information is available on the transcriptional profile of melatonin biosynthesizing enzyme genes in any tropical carp under either natural or artificial photothermal conditions in pineal and retina. The present study is an attempt to demonstrate the temporal pattern of expression of melatonin biosynthesizing enzyme genes, tryptophan hydroxylase 1 (tph1), arylalkylamine N-acetyltransferase (aanat1 and aanat2), and hydroxyindole-O-methyltransferase (hiomt) collectively and simultaneously in pineal organ and retina in tropical fish, C. catla, on a daily and seasonal basis under natural environmental conditions along with the serum melatonin levels. Depending upon the changes of the natural photothermal conditions, in four phases of an annual cycle, the variation and/or shifting of the rhythm parameters of different melatonin biosynthesizing enzyme genes in these two organs are different. Moreover, relative expression of these genes varies based on tissue and season. The serum melatonin levels correspond to the expression pattern of pineal aanat2 and hiomt. This finding indicates a possible organization of melatonin biosynthesizing enzyme genes with reproductive phases differently in these two photoreceptive organs for maintaining its physiological functions.

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Melatonin pathway: breaking the ‘high-at-night’ rule in trout retina

Cited by 70 publications

References 39 publications

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Drastic neofunctionalization associated with evolution of the timezyme AANAT 500 Mya

Retinal light input is required to sustain plasma melatonin rhythms in Nile tilapia Oreochromis niloticus niloticus

Daily and Seasonal Expression Profile of Serum Melatonin and Its Biosynthesizing Enzyme Genes (tph1, aanat1, aanat2, andhiomt) in Pineal Organ and Retina: A Study under Natural Environmental Conditions in a Tropical Carp,Catla catla

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