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Publication
Regulation of Glucose-Dependent Golgi-Derived Microtubules by cAMP/EPAC2
Promotes Secretory Vesicle Biogenesis in Pancreatic ß Cells.
Authors Trogden KP, Zhu X, Lee JS, Wright CVE, Gu G, Kaverina I
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Current biology : CB
Year 2019
Date Published 7/1/2019
Volume : Pages 29 : 2339 - 2350.e5
PubMed Reference 31303487
Abstract The microtubule (MT) network is an essential regulator of insulin secretion from
pancreatic ß cells, which is central to blood-sugar homeostasis. We find that
when glucose metabolism induces insulin secretion, it also increases formation
of Golgi-derived microtubules (GDMTs), notably with the same biphasic kinetics
as insulin exocytosis. Furthermore, GDMT nucleation is controlled by a glucose
signal-transduction pathway through cAMP and its effector EPAC2. Preventing new
GDMT nucleation dramatically affects the pipeline of insulin production,
storage, and release. There is an overall reduction of ß-cell insulin content,
and remaining insulin becomes retained within the Golgi, likely because of
stalling of insulin-granule budding. While not preventing glucose-induced
insulin exocytosis, the diminished granule availability substantially blunts the
amount secreted. Constant dynamic maintenance of the GDMT network is therefore
critical for normal ß-cell physiology. Our study demonstrates that the
biogenesis of post-Golgi carriers, particularly large secretory granules,
requires ongoing nucleation and replenishment of the GDMT network.




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