Selective nucleotide-release from dense-core granules in insulin-secreting cells

Author:

Obermüller Stefanie1,Lindqvist Anders1,Karanauskaite Jovita12,Galvanovskis Juris2,Rorsman Patrik12,Barg Sebastian13

Affiliation:

1. Department of Experimental Medicinal Sciences, Lund University, BMC B11, SE-221 84 Lund, Sweden

2. OCDEM, Nuffield Department of Clinical Medicine, University of Oxford, Churchill Hospital, Oxford, OX3 7LJ, UK

3. Vollum Institute, Oregon Health and Sciences University, 3181 SW Sam Jackson Park Road, Portland OR, 97210, USA

Abstract

Secretory granules of insulin-secreting cells are used to store and release peptide hormones as well as low-molecular-weight compounds such as nucleotides. Here we have compared the rate of exocytosis with the time courses of nucleotide and peptide release by a combination of capacitance measurements, electrophysiological detection of ATP release and single-granule imaging. We demonstrate that the release of nucleotides and peptides is delayed by ∼0.1 and ∼2 seconds with respect to membrane fusion, respectively. We further show that in up to 70% of the cases exocytosis does not result in significant release of the peptide cargo, likely because of a mechanism that leads to premature closure of the fusion pore. Release of nucleotides and protons occurred regardless of whether peptides were secreted or not. These observations suggest that insulin-secreting cells are able to use the same secretory vesicles to release small molecules either alone or together with the peptide hormone.

Publisher

The Company of Biologists

Subject

Cell Biology

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