2015
DOI: 10.1073/pnas.1409542112
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Aged insulin granules display reduced microtubule-dependent mobility and are disposed within actin-positive multigranular bodies

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 eit… Show more

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Cited by 72 publications
(99 citation statements)
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“…These data agree with the model where MTs and actin collaborate to drive non-directional insulin granule transport (Heaslip et al, 2014; Hoboth et al, 2015; Tabei et al, 2013), indicating that these conclusions from observations in cell lines can be extrapolated into three-dimensional granule transportation in intact islets. More importantly, we show that the ability of the cytoskeleton to displace granules does not correlate with high GSIS (Figure 4I).…”
Section: Resultssupporting
confidence: 84%
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“…These data agree with the model where MTs and actin collaborate to drive non-directional insulin granule transport (Heaslip et al, 2014; Hoboth et al, 2015; Tabei et al, 2013), indicating that these conclusions from observations in cell lines can be extrapolated into three-dimensional granule transportation in intact islets. More importantly, we show that the ability of the cytoskeleton to displace granules does not correlate with high GSIS (Figure 4I).…”
Section: Resultssupporting
confidence: 84%
“…This function is similar to actin-dependent restriction of transport described both for insulin granules (Heaslip et al, 2014; Hoboth et al, 2015) and pigment granules in melanocytes (Semenova et al, 2008; Wu et al, 1998). It is also clear that MTs tightly collaborate with the actin cytoskeleton to control insulin granule availability for secretion (Heaslip et al, 2014; Hoboth et al, 2015); here we show that, as a part of this interplay, actin influences the density of MT network in β cells. This possibly occurs because MT ends can be stabilized by actin-dependent capture (Gundersen et al, 2004).…”
Section: Discussionsupporting
confidence: 75%
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“…Initial confusion of the effect of these two agents has now been resolved by an elegant study demonstrating that their impact on stimulated insulin secretion depends on the stimulus, and specifically the origin of elevated cytosolic Ca 2ϩ , from outside the cell via voltage-gated channels or through mobilization of intracellular stores (46). There are, furthermore, two insulin granule pools that are differentially regulated through actin remodeling, depending again upon the source of Ca 2ϩ (45), and the rate of intracellular movement and of secretion of young and old insulin granules is modulated by actin coating (47). The role of the actin cytoskeleton and its dynamic remodeling following a secretory stimulus is thus even more complex than originally postulated, seeming to impact every aspect of the insulin exocytotic apparatus.…”
Section: Letting the Skeleton Out Of The Closetmentioning
confidence: 99%