Roles of Ca 2+ ions in the control of ChREBP nuclear translocation

Abstract

Carbohydrate-responsive element binding protein (ChREBP (MLXIPL)) is emerging as an importantmediator of glucotoxity both in the liver and in the pancreatic β-cells. Although the regulation of its nuclear translocation and transcriptional activation by glucose has been the subject of intensive research, it is still not fully understood. We have recently uncovered a novel mechanism in the excitable pancreatic β-cell where ChREBP interactswith sorcin, a penta-EF-handCa 2+-binding protein, and is sequestered in the cytosol at low glucose concentrations. Upon stimulation with glucose and activation of Ca 2+ influx, or application of ATP as an intracellular Ca 2+-mobilising agent, ChREBP rapidly translocates to the nucleus. In sorcin-silenced cells, ChREBP is constitutively present in the nucleus, and both glucose and Ca 2+ are ineffective in stimulating further ChREBP nuclear shuttling. Whether an active Ca 2+-sorcin element of ChREBP activation also exists in non-excitable cells is discussed. © 2012 Society for Endocrinology.