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Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E667-76. doi: 10.1073/pnas.1409542112. Epub 2015 Feb 2.

Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies.

Author information

1
Molecular Diabetology, Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, and German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany;
2
Department of Systems Immunology and Braunshweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
3
Department of Systems Immunology and Braunshweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany; Institute for Biochemistry, Biotechnology and Bioinformatics, Technische Universität Braunschweig, 38106 Braunschweig, Germany;
4
Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; and Faculty of Bioengineering and Bioinformatics, Moscow State University, 119234 Moscow, Russia.
5
Molecular Diabetology, Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital Carl Gustav Carus and Faculty of Medicine, Technische Universität Dresden, 01307 Dresden, and German Center for Diabetes Research (DZD e.V.), 85764 Neuherberg, Germany; Max Planck Institute of Molecular Cell Biology and Genetics, 01307 Dresden, Germany; and michele.solimena@tu-dresden.de.

Abstract

Insulin secretion is key for glucose homeostasis. Insulin secretory granules (SGs) exist in different functional pools, with young SGs being more mobile and preferentially secreted. However, the principles governing the mobility of age-distinct SGs remain undefined. Using the time-reporter insulin-SNAP to track age-distinct SGs we now show that their dynamics can be classified into three components: highly dynamic, restricted, and nearly immobile. Young SGs display all three components, whereas old SGs are either restricted or nearly immobile. Both glucose stimulation and F-actin depolymerization recruit a fraction of nearly immobile young, but not old, SGs for highly dynamic, microtubule-dependent transport. Moreover, F-actin marks multigranular bodies/lysosomes containing aged SGs. These data demonstrate that SGs lose their responsiveness to glucose stimulation and competence for microtubule-mediated transport over time while changing their relationship with F-actin.

KEYWORDS:

Bayesian probability theory; diabetes; islets; processivity; secretion

PMID:
25646459
PMCID:
PMC4343180
DOI:
10.1073/pnas.1409542112
[Indexed for MEDLINE]
Free PMC Article

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