Subfunctionalization of arylalkylamine N‐acetyltransferases in the sea bass Dicentrarchus labrax: two‐ones for one two

Abstract

Melatonin is an important component of the vertebrates circadian system, synthetized from serotonin by the successive action of the arylalkylamine N-acetyltransferase (Aanat: serotonin→N-acetylserotonin) and acetylserotonin-O-methyltransferase (Asmt: N-acetylserotonin→melatonin). Aanat is responsible for the daily rhythm in melatonin production. Teleost fish are unique because they express two Aanat genes, aanat1 and aanat2, mainly expressed in the retina and pineal gland, respectively. In silico analysis indicated that the teleost-specific whole-genome duplication generated Aanat1 duplicates (aanat1a and aanat1b); some fish express both of them, while others express either one of the isoforms. Here, we bring the first information on the structure, function, and distribution of Aanat1a and Aanat1b in a teleost, the sea bass Dicentrarchus labrax. Aanat1a and Aanat1b displayed a wide and distinct distribution in the nervous system and peripheral tissues, while Aanat2 appeared as a pineal enzyme. Co-expression of Aanats with asmt was found in the pineal gland and the three retinal nuclear layers. Enzyme kinetics indicated subtle differences in the affinity and catalytic efficiency of Aanat1a and Aanat1b for indolethylamines and phenylethylamines, respectively. Our data are consistent with the idea that Aanat2 is a pineal enzyme involved in melatonin production, while Aanat1 enzymes have a broader range of functions including melatonin synthesis in the retina, and catabolism of serotonin and dopamine in the retina and other tissues. The data are discussed in light of the recently uncovered roles of N-acetylserotonin and N-acetyldopamine as antioxidants, neuroprotectants, and modulators of cell proliferation and enzyme activities.

A Comparative Genomics Study on the Molecular Evolution of Serotonin/Melatonin Biosynthesizing Enzymes in Vertebrates

“…It was reported that the ASMT enzymes mainly exist in the retinae and pineal gland of European sea bass (Botros et al, 2013). ASMT2 was detected in several peripheral tissues, including liver and gut in teleosts (Paulin et al, 2015). The similar existence of melatonin synthesis in gut and liver of goldfish was demonstrated previously (Velarde et al, 2010a).…”

Two light‐activated neuroendocrine circuits arising in the eye trigger physiological and morphological pigmentation

“…One possibility is that melatonin provided by RGC axons targets melatonin receptors expressed at the retinotectal synapse. Chick RGCs synthetize melatonin and teleost RGCs express the key enzymes in melatonin synthesis (Garbarino‐Pico et al., ; Paulin et al., ). Further, exogenous melatonin represses depolarization‐dependent calcium signals in Xenopus tectal cells and calcium levels in RGC axons (Prada and Udin, ; Prada et al., ).…”

Daily Rhythm in Plasma N-acetyltryptamine

“…These include the pituitary gland and brain (Gaudet, Palkovits et al. 1991; Gaudet and Namboodiri 1993; Coon, Roseboom et al 1995; Coon, Mazuruk et al 1996; Fleming, Barrett et al 1999; Paulin, Cazamea-Catalan et al 2015). Further investigation is required to answer the question of whether activity increases at night in these tissues.…”

“…Similarly, it is possible that N-acetyltryptamine interactions with melatonin receptors in the vertebrate brain might also be involved in local signaling (Dubocovich 1991; Brooks and Cassone 1992; Davies, Hannah et al 1994; Dubocovich, Delagrange et al 2010; Paulin, Cazamea-Catalan et al 2015). One could envision such N-acetyltryptamine-mediated communication within discrete brain regions where abundance would be regulated through circadian clock driven cyclic AMP-dependent mechanisms similar to those which operate in the pineal gland and retina to control AANAT activity (Bernard, Klein et al 1997; Bolliet, Begay et al 1997; Iuvone, Tosini et al.…”