Journal
JOURNAL OF PHYSIOLOGY-LONDON
Volume 587, Issue 6, Pages 1169-1178Publisher
WILEY-BLACKWELL
DOI: 10.1113/jphysiol.2008.168005
Keywords
-
Categories
Funding
- A*STAR (Agency for Science, Technology and Research, Singapore)
- Biomedical Research Council
Ask authors/readers for more resources
Hormones such as glucagon are secreted by Ca2+-induced exocytosis of large dense-core vesicles, but the mechanisms involved have only been partially elucidated. Studies of pancreatic beta-cells secreting insulin revealed that synaptotagmin-7 alone is not sufficient to mediate Ca2+-dependent insulin granule exocytosis, and studies of chromaffin cells secreting neuropeptides and catecholamines showed that synaptotagmin-1 and -7 collaborate as Ca2+ sensors for exocytosis, and that both are equally involved. As no other peptide secretion was analysed, it remains unclear whether synaptotagmins generally act as Ca2+ sensors in large dense-core vesicle exocytosis in endocrine cells, and if so, whether synaptotagmin-7 always functions with a partner in that role. In particular, far less is known about the mechanisms underlying Ca2+-triggered glucagon release from alpha-cells than insulin secretion from beta-cells, even though insulin and glucagon together regulate blood glucose levels. To address these issues, we analysed the role of synaptotagmins in Ca2+-triggered glucagon exocytosis. Surprisingly, we find that deletion of a single synaptotagmin isoform, synaptotagmin-7, nearly abolished Ca2+-triggered glucagon secretion. Moreover, single-cell capacitance measurements confirmed that pancreatic alpha-cells lacking synaptotagmin-7 exhibited little Ca2+-induced exocytosis, whereas all other physiological and morphological parameters of the alpha-cells were normal. Our data thus identify synaptotagmin-7 as a principal Ca2+ sensor for glucagon secretion, and support the notion that synaptotagmins perform a universal but selective function as individually acting Ca2+ sensors in neurotransmitter, neuropeptide, and hormone secretion.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available