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Hoboth, P. ; Müller, A. ; Ivanova, A. ; Mziaut, H. ; Dehghany, J.* ; Sönmez, A. ; Lachnit, M. ; Meyer-Hermann, M.* ; Kalaidzidis, Y.* ; Solimena, M.

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

Proc. Natl. Acad. Sci. U.S.A. 112, E667-E676 (2015)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Bayesian Probability Theory ; Diabetes ; Islets ; Processivity ; Secretion; Pancreatic Beta-cell; Molecules In-vivo; Secretory Granules; Fusion Proteins; O-6-alkylguanine-dna Alkyltransferase; Microfilamentous System; Diabetes-mellitus; Glucose-tolerance; Rat Pancreas; B-cell
Language english
Publication Year 2015
HGF-reported in Year 2015
ISSN (print) / ISBN 0027-8424
e-ISSN 1091-6490
Journal Proceedings of the National Academy of Sciences of the United States of America
Quellenangaben Volume: 112, Issue: 7, Pages: E667-E676 Article Number: , Supplement: ,
Publisher National Academy of Sciences
Publishing Place Washington
Reviewing status Peer reviewed
Institute(s) Institute of Pancreatic Islet Research (IPI)
POF-Topic(s) 90000 - German Center for Diabetes Research
Research field(s) Helmholtz Diabetes Center
PSP Element(s) G-502600-001
PubMed ID 25646459
DOI 10.1073/pnas.1409542112
WOS ID WOS:000349446000010
Erfassungsdatum 2015-02-05
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