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- Title
Deletion of the secretory vesicle proteins IA-2 and IA-2β disrupts circadian rhythms of cardiovascular and physical activity.
- Authors
Soo Mi Kim; Power, Andrea; Brown, Timothy M.; Constance, Cara M.; Coon, Steven L.; Nishimura, Takuya; Hirai, Hiroki; Cai, Tao; Eisner, Christoph; Weaver, David R.; Piggins, Hugh D.; Klein, David C.; Schnermann, Jürgen; Notkins, Abner L.
- Abstract
Targeted deletion of IA-2 and IA-2β, major autoantigens in type 1 diabetes and transmembrane secretory vesicle proteins, results in impaired secretion of hormones and neurotransmitters. In the present study, we evaluated the effect of these deletions on daily rhythms in blood pressure, heart rate, core body temperature, and spontaneous physical and neuronal activity. We found that deletion of both IA-2 and IA-213 profoundly disrupts the usual diurnal variation of each of these parameters, whereas the deletion of either IA-2 or IA-213 alone did not produce a major change. In situ hybridization revealed that IA-2 and IA-213 transcripts are highly but nonrhythmically expressed in the suprachiasmatic nuclei, the site of the brain's master circadian oscillator. Electrophysiological studies on tissue slices from the suprachiasmatic nuclei showed that disruption of both IA-2 and IA-213 results in significant alterations in neuronal firing. From these studies, we concluded that deletion of IA-2 and IA-2β, structural proteins of secretory vesicles and modulators of neuroendocrine secretion, has a profound effect on the circadian system.
- Subjects
ANTIGENS; CIRCADIAN rhythms; CARDIOVASCULAR system physiology; PHYSICAL fitness; BLOOD pressure; HEART beat; BODY temperature; HORMONES
- Publication
FASEB Journal, 2009, Vol 23, Issue 9, p3226
- ISSN
0892-6638
- Publication type
Article
- DOI
10.1096/fj.09-132019