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J Biol Chem, Vol. 274, Issue 29, 20628-20632, July 16, 1999

The C Terminus of SUR1 Is Required for Trafficking of K_ATP Channels

Nidhi Sharma, Ana Crane^§, John P. Clement IV^§, Gabriela Gonzalez^§, Andrey P. Babenko^§, Joseph Bryan^§, and Lydia Aguilar-Bryan

From the Departments of  Medicine and ^§ Cell Biology, Baylor College of Medicine, Houston, Texas 77030

In beta cells from the pancreas, ATP-sensitive potassium channels, or K_ATP channels, are composed of two subunits, SUR1 and K_IR6.2, assembled in a (SUR1/K_IR6.2)₄ stoichiometry. The correct stoichiometry of channels at the cell surface is tightly regulated by the presence of novel endoplasmic reticulum (ER) retention signals in SUR1 and K_IR6.2; incompletely assembled K_ATP channels fail to exit the ER/cis-Golgi compartments. In addition to these retrograde signals, we show that the C terminus of SUR1 has an anterograde signal, composed in part of a dileucine motif and downstream phenylalanine, which is required for K_ATP channels to exit the ER/cis-Golgi compartments and transit to the cell surface. Deletion of as few as seven amino acids, including the phenylalanine, from SUR1 markedly reduces surface expression of K_ATP channels. Mutations leading to truncation of the C terminus of SUR1 are one cause of a severe, recessive form of persistent hyperinsulinemic hypoglycemia of infancy. We propose that the complete loss of beta cell K_ATP channel activity seen in this form of hyperinsulinism is a failure of K_ATP channels to traffic to the plasma membrane.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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