NeuroD1 protein dynamics in the developing and adult rat pineal gland

CASTRO A; IBAÑEZ P; BENITEZ SG; PLANO SA; KLEIN D; MUÑOZ EM

Mendoza

Congreso; XII Latin American Symposium on Chronobiology; 2013

NeuroD1 is a bHLH transcription factor involved in the establishment and maintenance of specific endocrine and neuronal phenotypes. We previously reported that NeuroD1 mRNA is present in the developing and adult rodent pineal gland and that the transcript levels were not under sympathetic neural influence. Global transcriptome analysis of two different KO mice revealed potential NeuroD1 target genes in retina and pineal gland. Here, we report the first NeuroD1 protein characterization in the rat pineal gland. Ontogenetic expression of NeuroD1 protein follows the previously reported mRNA pattern. NeuroD1 is nuclear in embryonic and neonatal stages. From there, NeuroD1 protein is present in pinealocyte nuclei mainly at early night (ZT14) and it is cytoplasmic during daytime (ZT6). This rhythmic pattern in NeuroD1 subcellular localization is maintained during adulthood. Additionally, the nuclear localization of NeuroD1 was affected after disruption of the sympathetic innervation via SCGx and by in vivo administration of α- and β-adrenoceptor antagonists. Study of NeuroD1 phosphorylation state revealed that two serine residues, Ser274 and Ser336, result modifiable. These data suggest that NeuroD1 protein might influence the pineal biology in a circadian manner and that phosphorylation mechanisms might be involved.