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Review
. 2013 Sep 18:4:124.
doi: 10.3389/fendo.2013.00124.

The functional significance of synaptotagmin diversity in neuroendocrine secretion

Paanteha K Moghadam  1 , Meyer B Jackson
Affiliations
Review

The functional significance of synaptotagmin diversity in neuroendocrine secretion

Paanteha K Moghadam et al. Front Endocrinol (Lausanne). .

Abstract

Synaptotagmins (syts) are abundant, evolutionarily conserved integral membrane proteins that play essential roles in regulated exocytosis in nervous and endocrine systems. There are at least 17 syt isoforms in mammals, all with tandem C-terminal C2 domains with highly variable capacities for Ca(2+) binding. Many syts play roles in neurotransmitter release or hormone secretion or both, and a growing body of work supports a role for some syts as Ca(2+) sensors of exocytosis. Work in many types of endocrine cells has documented the presence of a number of syt isoforms on dense-core vesicles containing various hormones. Syts can influence the kinetics of exocytotic fusion pores and the choice of release mode between kiss-and-run and full-fusion. Vesicles harboring different syt isoforms can preferentially undergo distinct modes of exocytosis with different forms of stimulation. The diverse properties of syt isoforms enable these proteins to shape Ca(2+) sensing in endocrine cells, thus contributing to the regulation of hormone release and the organization of complex endocrine functions.

Keywords: calcium; dense-core vesicle; exocytosis; fusion pores; insulin; kiss-and-run; neuropeptides; norepinephrine.

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Figures

Figure 1
Figure 1
Ca2+ domains and release mechanisms. (A) Weak stimulation opens Ca2+ channels less frequently. One isolated channel can open and as Ca2+ flows a domain of high Ca2+ concentration will form around the channel mouth. This will lead to a highly localized Ca2+ signal that will persist for milliseconds. A Ca2+ sensor such as syt 1, with its rapid kinetics and low affinity, can be activated by a Ca2+ signal of this form. (B) Strong stimulation opens many Ca2+ channels to raise bulk Ca2+. Bulk Ca2+ can also rise as a result of Ca2+ release from internal stores. After the stimulus ends the Ca2+ gradients around individual vesicles will collapse as Ca2+ diffuses through the cytoplasm away from the membrane. This will lead to a more uniform, moderate concentration that can persist for seconds. A Ca2+ sensor such as syt 7, with its slow kinetics and high affinity, can be activated by a Ca2+ signal of this form.
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