Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01275 (glucagon)
 26,492 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Synaptotagmins (Syts) III, V, VI, and X are classified as a subclass of Syt, based on their sequence similarities and biochemical properties (Ibata, K., Fukuda, M., and Mikoshiba, K. (1998) J. Biol. Chem. 273, 12267-12273; Fukuda, M., Kanno, E., and Mikoshiba, K. (1999) J. Biol. Chem. 274, 31421-31427). Although they have been suggested to be involved in vesicular trafficking, as in the role of the Syt I isoform in synaptic vesicle exocytosis, their exact functions remain to be clarified, and even their precise subcellular localization is still a matter of controversy. In this study, we established rat pheochromocytoma (PC12) cell lines that stably express Syts III-, V-, VI-, and X-GFP (green fluorescence protein) fusion proteins, respectively, to determine their precise subcellular localizations. Surprisingly, Syts III-, V-, VI-, and X-GFP proteins were found to be targeted to specific organelles: Syt III-GFP to near the plasma membrane, Syt V-GFP to dense-core vesicles, Syt VI-GFP to endoplasmic reticulum-like structures, and Syt X-GFP to vesicles (other than dense-core vesicles) present in cytoplasm. We showed that Syt V-containing vesicles at the neurites of PC12 cells were processed to exocytosis in a Ca2+-dependent manner. Immunohistochemical analysis further showed that endogenous Syt V was also localized on dense-core vesicles in the mouse brain and specifically expressed in glucagon-positive alpha-cells in mouse pancreatic islets, but not in beta- or delta-cells. Based on these results, we propose that Syt V is a dense-core vesicle-specific Syt isoform that controls a specific type of Ca2+-regulated secretion.
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PMID:Synaptotagmin V is targeted to dense-core vesicles that undergo calcium-dependent exocytosis in PC12 cells. 1200 94

Synaptotagmin (Syt) is involved in Ca2+ -regulated secretion and has been suggested to serve as a general Ca2+ sensor on the membrane of secretory vesicles in neuronal cells. Insulin exocytosis from the pancreatic beta-cell is an example of a Ca2+ -dependent secretory process. Previous studies have yielded conflicting results as to which Syt isoform is present on the secretory granules in the native beta-cell. Here we show by western blotting and RT-PCR analysis, the presence of both Syt V and Syt IX in rat pancreatic islets and in the clonal beta-cell line INS-1E. The subcellular distribution of the two Syt isoforms was assessed by confocal microscopy and by sedimentation in a continuous sucrose density gradient in INS-1E cells. These experiments show that both proteins colocalize with insulin-containing secretory granules but are absent from synaptic-like microvesicles. Further immunofluorescence studies performed in primary pancreatic endocrine cells revealed that Syt V is present in glucagon-secreting alpha-cells, whereas Syt IX is associated with insulin granules in beta-cells. Transient overexpression of Syt V and Syt IX did not alter exocytosis in INS-1E cells. Finally, reduction of the expression of both Syt isoforms by RNA interference did not change basal secretion. Remarkably, hormone release in response to glucose was selectively and strongly reduced, indicating that Syt V and Syt IX are directly involved in the Ca2+ -dependent stimulation of exocytosis.
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PMID:Synaptotagmin V and IX isoforms control Ca2+ -dependent insulin exocytosis. 1519 Jan 21