%0 Journal Article
%T Magel2, a Prader-Willi syndrome candidate gene, modulates the activities of circadian rhythm proteins in cultured cells
%A Julia Devos
%A Sara V Weselake
%A Rachel Wevrick
%J Journal of Circadian Rhythms
%D 2011
%I BioMed Central
%R 10.1186/1740-3391-9-12
%X We used a variety of cell-based assays to determine whether Magel2 modifies the properties of core circadian rhythm proteins.Magel2 represses the activity of the Clock:Bmal1 heterodimer in a Per2-luciferase assay. Magel2 interacts with Bmal1 and with Per2 as measured by co-immunoprecipitation in co-transfected cells, and exhibits a subcellular distribution consistent with these interactions when visualized by immunofluorescence. As well, Magel2 induces the redistribution of the subcellular localization of Clock towards the cytoplasm, in contrast to the nucleus-directed effect of Bmal1 on Clock subcellular localization.Consistent with the blunted circadian rhythm observed in Magel2-null mice, these data suggest that Magel2 normally promotes negative feedback regulation of the cellular circadian cycle, through interactions with key core circadian rhythm proteins.Prader-Willi syndrome (PWS) is a genetic neurodevelopmental disorder featuring neonatal failure to thrive, hyperphagia leading to obesity, growth hormone deficiency, and other findings [1-3]. About 80% of affected individuals suffer from sleep-wake cycle disturbances, typically characterized as excessive daytime sleepiness, with night or early morning waking [4]. These clinical findings implicate hypothalamic dysfunction in PWS, but the pathophysiology of this disorder remains poorly understood, in part because at least five genes are inactivated in typical affected individuals. We identified MAGEL2, a member of the necdin/MAGE protein family, as a candidate gene for some features of PWS [2,3]. In adult mice, Magel2 expression is restricted to the nervous system, with the majority of Magel2-positive neurons located in the hypothalamus [5]. Within the hypothalamus, Magel2 is primarily expressed in the paraventricular nucleus, supraoptic nucleus, and in the suprachiasmatic nucleus (SCN), which is the circadian rhythm generating center of the brain [6]. Within the SCN, Magel2-positive neurons overlap with neurons
%K suprachiasmatic nucleus
%K Prader-Willi syndrome
%K luciferase assay
%K melanoma antigen gene
%K necdin
%U http://www.jcircadianrhythms.com/content/9/1/12