Kv2.1 Clustering Contributes to Insulin Exocytosis and Rescues Human β-Cell Dysfunction.

ABSTRACT: Insulin exocytosis is regulated by ion channels that control excitability and Ca²⁺ influx. Channels also play an increasingly appreciated role in microdomain structure. In this study, we examine the mechanism by which the voltage-dependent K⁺ (Kv) channel Kv2.1 (KCNB1) facilitates depolarization-induced exocytosis in INS 832/13 cells and β-cells from human donors with and without type 2 diabetes (T2D). We find that Kv2.1, but not Kv2.2 (KCNB2), forms clusters of 6-12 tetrameric channels at the plasma membrane and facilitates insulin exocytosis. Knockdown of Kv2.1 expression reduces secretory granule targeting to the plasma membrane. Expression of the full-length channel (Kv2.1-wild-type) supports the glucose-dependent recruitment of secretory granules. H

SUBMITTER: Fu J 

PROVIDER: S-EPMC5482075 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature