Near-UV Light Induced ROS Production Initiates Spatial Ca<sup>2+</sup> Spiking to Fire NFATc3 Translocation.

Overview

Ca²⁺-dependent gene regulation controls several functions to determine the fate of the cells. Proteins of the nuclear factor of activated T-cells (NFAT) family are Ca²⁺ sensitive transcription factors that control the cell growth, proliferation and insulin secretion in β-cells. Translocation of NFAT proteins to the nucleus occurs in a sequence of events that starts with activating calmodulin-dependent phosphatase calcineurin in a Ca²⁺-dependent manner, which dephosphorylates the NFAT proteins and leads to their translocation to the nucleus. Here, we examined the role of IP₃-generating agonists and near-UV light in the induction of NFATc3 migration to the nucleus in the pancreatic β-cell line INS-1. Our results show that IP₃ generation yields cytosolic Ca²⁺ rise and NFATc3 translocation. Moreover, near-UV light exposure generates reactive oxygen species (ROS), resulting in cytosolic Ca²⁺ spiking via the L-type Ca²⁺ channel and triggers NFATc3 translocation to the nucleus. Using the mitochondria as a Ca²⁺ buffering tool, we showed that ROS-induced cytosolic Ca²⁺ spiking, not the ROS themselves, was the triggering mechanism of nuclear import of NFATc3. Collectively, this study reveals the mechanism of near-UV light induced NFATc3 migration.