Deletion of the secretory vesicle proteins IA-2 and IA-2beta disrupts circadian rhythms of cardiovascular and physical activity
Authors
Kim, Soo MiPower, Andrea
Coon, Steven L.
Constance, Cara M.
Nishimura, Takuya
Hirai, Hiroki
Cai, Tao
Eisner, Christoph
Weaver, David R.
Piggins, Hugh D.
Klein, David C.
Schnermann, Jurgen
Notkins, Abner L.
Document Type
Journal ArticlePublication Date
2009-09-01Keywords
Animals*Circadian Rhythm
*Electrophysiology
Hemodynamics
Mice
RNA, Messenger
Receptor-Like Protein Tyrosine Phosphatases, Class
8
Secretory Vesicles
Suprachiasmatic Nucleus
Neuroscience and Neurobiology
Metadata
Show full item recordAbstract
Targeted deletion of IA-2 and IA-2beta, 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-2beta profoundly disrupts the usual diurnal variation of each of these parameters, whereas the deletion of either IA-2 or IA-2beta alone did not produce a major change. In situ hybridization revealed that IA-2 and IA-2beta 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-2beta results in significant alterations in neuronal firing. From these studies, we concluded that deletion of IA-2 and IA-2beta, structural proteins of secretory vesicles and modulators of neuroendocrine secretion, has a profound effect on the circadian system.Source
FASEB J. 2009 Sep;23(9):3226-32. Epub 2009 May 11. Link to article on publisher's siteDOI
10.1096/fj.09-132019Permanent Link to this Item
http://hdl.handle.net/20.500.14038/37992PubMed ID
19433624Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1096/fj.09-132019