KATP channels (ATP-sensitive potassium channels), comprising four subunits each of Kir6.2 (inwardly rectifying potassium channel 6.2) and the SUR1 (sulfonylurea receptor 1), play a central role in glucose-stimulated insulin secretion by the pancreatic β-cell. Changes in the number of channels at the cell surface are associated with genetic diseases of aberrant insulin secretion, including CHI (congenital hyperinsulinism) and NDM (neonatal diabetes mellitus). The present review summarizes advances in our understanding of the vesicular trafficking of normal KATP channels and how genetic mutations in Kir6.2 interfere with such trafficking. A mutation, E282K, causing CHI, was found to disrupt a DXE [di-acidic ER (endoplasmic reticulum)-exit signal], thereby preventing its assembly into COPII (coatamer protein II)-coated vesicles and subsequent ER exit. The resultant decrease in the cell-surface density of the channel could explain the disease phenotype. Two mutations, Y330C and F333I, reported in patients with NDM, disrupted an endocytic traffic signal, thereby impairing CCV (clathrin-coated vesicle) formation and endocytosis. The consequent increase in the density of KATP channels, together with an attenuated sensitivity to ATP reported previously, may account for the severe form of NDM.
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November 2007
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Conference Article|
October 25 2007
Trafficking of ATP-sensitive potassium channels in health and disease
A. Sivaprasadarao;
A. Sivaprasadarao
1
1Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
1To whom correspondence should be addressed (email a.sivaprasadarao@leeds.ac.uk).
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T.K. Taneja;
T.K. Taneja
1Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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J. Mankouri;
J. Mankouri
1Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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A.J. Smith
A.J. Smith
1Institute of Membrane and Systems Biology, Faculty of Biological Sciences, University of Leeds, Leeds LS2 9JT, U.K.
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Publisher: Portland Press Ltd
Received:
June 11 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (5): 1055–1059.
Article history
Received:
June 11 2007
Citation
A. Sivaprasadarao, T.K. Taneja, J. Mankouri, A.J. Smith; Trafficking of ATP-sensitive potassium channels in health and disease. Biochem Soc Trans 1 November 2007; 35 (5): 1055–1059. doi: https://doi.org/10.1042/BST0351055
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