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- Olsen, HL, et al.
(författare)
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Phosphatidylinositol 4-kinase serves as a metabolic sensor and regulates priming of secretory granules in pancreatic beta cells
- 2003
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Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 100:9, s. 5187-5192
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Tidskriftsartikel (refereegranskat)abstract
- Insulin secretion is controlled by the beta cell's metabolic state, and the ability of the secretory granules to undergo exocytosis increases during glucose stimulation in a membrane potential-independent fashion. Here, we demonstrate that exocytosis of insulin-containing secretory granules depends on phosphatidylinositol 4-kinase (PI 4-kinase) activity and that inhibition of this enzyme suppresses glucose-stimulated insulin secretion. Intracellular application of phosphaticlylinositol 4-phosphate and phosphatidylinositol 4,5-bisphosphate [Pl(4,5)P-2] stimulated exocytosis by promoting the priming of secretory granules for release and increasing the number of granules residing in a readily releasable pool. Reducing the cytoplasmic ADP concentration in a way mimicking the effects of glucose stimulation activated PI 4-kinase and increased exocytosis whereas changes of the ATP concentration in the physiological range had little effect. The PI(4,5)P-2-binding protein Ca2+-dependent activator protein for secretion (CAPS) is present in beta cells, and neutralization of the protein abolished both Ca2+- and PI(4,5)P-2-induced exocytosis. We conclude that ADP-induced changes in PI 4-kinase activity, via generation of Pl(4,5)P-2, represents a metabolic sensor in the beta cell by virtue of its capacity to regulate the release competence of the secretory granules.
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- Bertorello, AM, et al.
(författare)
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Analysis of Na+,K+-ATPase motion and incorporation into the plasma membrane in response to G protein-coupled receptor signals in living cells
- 2003
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Ingår i: Molecular biology of the cell. - : American Society for Cell Biology (ASCB). - 1059-1524 .- 1939-4586. ; 14:3, s. 1149-1157
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Tidskriftsartikel (refereegranskat)abstract
- Dopamine (DA) increases Na+,K+-ATPase activity in lung alveolar epithelial cells. This effect is associated with an increase in Na+,K+-ATPase molecules within the plasma membrane ( Ridge et al., 2002 ). Analysis of Na+,K+-ATPase motion was performed in real-time in alveolar cells stably expressing Na+,K+-ATPase molecules carrying a fluorescent tag (green fluorescent protein) in the α-subunit. The data demonstrate a distinct (random walk) pattern of basal movement of Na+,K+-ATPase–containing vesicles in nontreated cells. DA increased the directional movement (by 3.5 fold) of the vesicles and an increase in their velocity (by 25%) that consequently promoted the incorporation of vesicles into the plasma membrane. The movement of Na+,K+-ATPase–containing vesicles and incorporation into the plasma membrane were microtubule dependent, and disruption of this network perturbed vesicle motion toward the plasma membrane and prevented the increase in the Na+,K+-ATPase activity induced by DA. Thus, recruitment of new Na+,K+-ATPase molecules into the plasma membrane appears to be a major mechanism by which dopamine increases total cell Na+,K+-ATPase activity.
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