Hoboth Peter, Müller Andreas, Ivanova Anna, Mziaut Hassan, Dehghany Jaber, Sönmez Anke, Lachnit Martina, Meyer-Hermann Michael, Kalaidzidis Yannis, Solimena Michele
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;
Department of Systems Immunology and Braunshweig Integrated Centre of Systems Biology, Helmholtz Centre for Infection Research, 38124 Braunschweig, Germany;
Proc Natl Acad Sci U S A. 2015 Feb 17;112(7):E667-76. doi: 10.1073/pnas.1409542112. Epub 2015 Feb 2.
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.
胰岛素分泌是葡萄糖稳态的关键。胰岛素分泌颗粒（SGs）存在于不同的功能池中，年轻的SGs更具流动性且优先分泌。然而，决定不同年龄SGs流动性的机制仍不明确。利用时间报告胰岛素-SNAP来追踪不同年龄的SGs，我们现在表明它们的动态可分为三个成分：高动态、受限和几乎不动。年轻的SGs表现出所有三个成分，而老的SGs要么受限要么几乎不动。葡萄糖刺激和F-肌动蛋白解聚都会募集一部分几乎不动的年轻SGs（而非老的SGs）进行高动态、微管依赖的运输。此外，F-肌动蛋白标记含有老化SGs的多颗粒体/溶酶体。这些数据表明，随着时间的推移，SGs对葡萄糖刺激的反应性和微管介导运输的能力丧失，同时改变了它们与F-肌动蛋白的关系。
