Role of Two-Pore Channels in Embryonic Development and Cellular Differentiation

Since the identification of nicotinic acid adenine dinucleotide phosphate (NAADP) and its putative target, the two-pore channel (TPC), the NAADP/TPC/Ca 2+ signaling pathway has been reported to play a role in a diverse range of functions in a variety of different cell types. TPCs have also been associated with a number of diseases, which arise when their activity is perturbed. In addition, TPCs have been shown to play key roles in various embryological processes and during the differentiation of a variety of cell types. Here, we review the role of NAADP/TPC/Ca 2+ signaling during early embryonic development and cellular differentiation. We pay particular attention to the role of TPC2 in the development and maturation of early neuromuscular activity in zebrafish, and during the differentiation of isolated osteoclasts, endothelial cells, and keratinocytes. Our aim is to emphasize the conserved features of TPC-mediated Ca 2+ signaling in a number of selected examples.