Synaptotagmin-7 is a principal Ca2+ sensor for Ca2+ -induced glucagon exocytosis in pancreas.

Journal article

Hormones such as glucagon are secreted by Ca(2+)-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 Ca(2+)-dependent insulin granule exocytosis, and studies of chromaffin cells secreting neuropeptides and catecholamines showed that synaptotagmin-1 and -7 collaborate as Ca(2+) sensors for exocytosis, and that both are equally involved. As no other peptide secretion was analysed, it remains unclear whether synaptotagmins generally act as Ca(2+) 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 Ca(2+)-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 Ca(2+)-triggered glucagon exocytosis. Surprisingly, we find that deletion of a single synaptotagmin isoform, synaptotagmin-7, nearly abolished Ca(2+)-triggered glucagon secretion. Moreover, single-cell capacitance measurements confirmed that pancreatic alpha-cells lacking synaptotagmin-7 exhibited little Ca(2+)-induced exocytosis, whereas all other physiological and morphological parameters of the alpha-cells were normal. Our data thus identify synaptotagmin-7 as a principal Ca(2+) sensor for glucagon secretion, and support the notion that synaptotagmins perform a universal but selective function as individually acting Ca(2+) sensors in neurotransmitter, neuropeptide, and hormone secretion.

Authors: Gustavsson, N; Wei, S; Hoang, D; Lao, Y; Zhang, Q

• Publication status: Published
• Journal: Journal of physiology
• Volume: 587
• Issue: Pt 6
• Pages: 1169-1178
• Publication date: 2009-03-01
• DOI: 10.1113/jphysiol.2008.168005
• EISSN: 1469-7793
• ISSN: 0022-3751
• Language: English
• Keywords: Exocytosis; Animals; Mice, Inbred Strains; Mice; omega-Conotoxins; Islets of Langerhans; Action Potentials; Insulin; Synaptotagmins; Blood Glucose; Hypoglycemia; Male; Intracellular Calcium-Sensing Proteins; Gene Expression; Calcium Channels; Glucagon-Secreting Cells; Mice, Knockout; Glucagon