Regulation of arylalkylamine N-acetyltransferase-2 (AANAT2, EC 2.3.1.87) in the fish pineal organ: Evidence for a role of proteasomal proteolysis

In fish, individual photoreceptor cells in the pineal organ and retina cont ain complete melatonin rhythm generating systems. In the pike and seabream, this includes a photodetector, circadian clock, and melatonin synthesis ma chinery; the trout lacks a functional clock. The melatonin rhythm is due in part to a nocturnal increase in the activity of the arylalkylamine N-acety ltransferase (AANAT) which is inhibited by light. Two AANATs have been iden tified in fish: AANAT1, more closely related to AANATs found in higher vert ebrates, is specifically expressed in the retina; AANAT2 is specifically ex pressed in the pineal organ. We show that there is a physiological day/nigh t rhythm in pineal AANAT2 protein in the pike, and that light exposure at m idnight decreases the abundance of AANAT2 protein and activity. In culture, this decrease is blocked by inhibitors of the proteasomal degradation path way. If glands are maintained under light at night, treatment with these in hibitors increases AANAT2 activity and protein. Organ culture studies with the trout and seabream also indicate that the light-induced decrease of AAN AT2 activity is prevented when proteasomal proteolysis is blocked. A cAMP-d ependent pathway protects AANAT2 protein from degradation. These results pr ovide a clue to understanding how light regulates the daily rhythm in melat onin secretion in Gsh photoreceptor cells and provides evidence that protea somal proteolysis is a conserved element in the regulation of AANAT in vert ebrates.