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Deletion of the secretory vesicle proteins IA‐2 and IA‐2β disrupts circadian rhythms of cardiovascular and physical activity
Author(s) -
Kim Soo Mi,
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,
Notions Abner L.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-132019
Subject(s) - circadian rhythm , endocrinology , secretion , biology , medicine , secretory vesicle , vesicle , hormone , chemistry , microbiology and biotechnology , biochemistry , exocytosis , membrane
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‐2β profoundly disrupts the usual diurnal variation of each of these parameters, whereas the deletion of either IA‐2 or IA‐2β alone did not produce a major change. In situ hybridization revealed that IA‐2 and IA‐2β 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‐2β 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.—Kim, S. M., Power, A., Brown, T. M., Constance, C. M., Coon, S. L., Nishimura, T., Hirai, H., Cai, T., Eisner, C., Weaver, D. R., Piggins, H. D., Klein, D. C., Schnermann, J., Notkins, A. L. Deletion of the secretory vesicle proteins IA‐2 and IA‐2β disrupts circadian rhythms of cardiovascular and physical activity. FASEBJ . 23, 3226‐3232 (2009). www.fasebj.org