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• W2921116500 abstract "Abstract Two key prerequisites for glucose stimulated insulin secretion (GSIS) in Beta cells are the proximity of insulin granules to the plasma membrane and their anchoring or docking to the plasma membrane (PM). While recent evidence has indicated that both of these factors are altered in the context of diabetes, it is unclear what regulates localization of insulin and its interactions with the PM within single cells. Here we demonstrate that microtubule (MT) motor mediated transport dynamics have a critical role in regulating both factors. Super-resolution imaging shows that while the MT cytoskeleton resembles a random meshwork in the cells’ interior, MTs near the cells surface are preferentially aligned with the PM. Computational modeling demonstrates two consequences of this alignment. First, this structured MT network preferentially withdraws granules from the PM. Second, the binding and transport of insulin granules by MT motors prevents their stable anchoring to the PM. The MT cytoskeleton thus negatively regulates GSIS by both limiting the amount of insulin proximal to the PM and preventing/breaking interactions between the PM and the remaining nearby insulin. These results predict that altering MT structure in beta cells can be used to tune GSIS. Thus, our study points to a potential of an alternative therapeutic strategy for diabetes by targeting specific MT regulators." @default.
• W2921116500 created "2019-03-22" @default.
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• W2921116500 date "2019-03-18" @default.
• W2921116500 modified "2023-10-16" @default.
• W2921116500 title "Microtubules Regulate Spatial Localization and Availability of Insulin Granules in Pancreatic Beta Cells" @default.
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• W2921116500 doi "https://doi.org/10.1101/581330" @default.
• W2921116500 hasPublicationYear "2019" @default.
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