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Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Am+J+Physiol+Endocrinol+Metab 2011 ; 300 (2): E276-86 Nephropedia Template TP
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?-Synuclein binds the KATP channel at insulin-secretory granules and inhibits insulin secretion #MMPMID20858756
Geng X; Lou H; Wang J; Li L; Swanson AL; Sun M; Beers-Stolz D; Watkins S; Perez RG; Drain P
Am J Physiol Endocrinol Metab 2011[Feb]; 300 (2): E276-86 PMID20858756show ga
?-Synuclein has been studied in numerous cell types often associated with secretory processes. In pancreatic ?-cells, ?-synuclein might therefore play a similar role by interacting with organelles involved in insulin secretion. We tested for ?-synuclein localizing to insulin-secretory granules and characterized its role in glucose-stimulated insulin secretion. Immunohistochemistry and fluorescent sulfonylureas were used to test for ?-synuclein localization to insulin granules in ?-cells, immunoprecipitation with Western blot analysis for interaction between ?-synuclein and KATP channels, and ELISA assays for the effect of altering ?-synuclein expression up or down on insulin secretion in INS1 cells or mouse islets, respectively. Differences in cellular phenotype between ?-synuclein knockout and wild-type ?-cells were found by using confocal microscopy to image the fluorescent insulin biosensor Ins-C-emGFP and by using transmission electron microscopy. The results show that anti-?-synuclein antibodies labeled secretory organelles within ?-cells. Anti-?-synuclein antibodies colocalized with KATP channel, anti-insulin, and anti-C-peptide antibodies. ?-Synuclein coimmunoprecipitated in complexes with KATP channels. Expression of ?-synuclein downregulated insulin secretion at 2.8 mM glucose with little effect following 16.7 mM glucose stimulation. ?-Synuclein knockout islets upregulated insulin secretion at 2.8 and 8.4 mM but not 16.7 mM glucose, consistent with the depleted insulin granule density at the ?-cell surface membranes observed in these islets. These findings demonstrate that ?-synuclein interacts with KATP channels and insulin-secretory granules and functionally acts as a brake on secretion that glucose stimulation can override. ?-Synuclein might play similar roles in diabetes as it does in other degenerative diseases, including Alzheimer's and Parkinson's diseases.
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Am+J+Physiol+Endocrinol+Metab 2011 ; 300 (2): E276-86
