International research collaborators have identified a new family of proteins, TPC2 (two-pore channels), that facilitates calcium signaling from specialized subcellular organelles.
The study, published today in Nature , is the first to isolate TPC2 as a channel that binds to nucleotide nicotinic acid adenine dinucleotide phosphate (NAADP), a second-signaling messenger, resulting in the release of calcium from intracellular stores. According to the researchers, this new discovery may have broad implications in cell biology and human disease research.
“The discovery was the result of many researchers working as one international team toward a unified outcome. We are very appreciative of all the collaborators' efforts,” said Jianjie Ma, PhD, professor of physiology and biophysics at UMDNJ-Robert Wood Johnson Medical School. “We are proud to be part of a study that will stand as the foundation for further exploration of human disease, helping researchers to better understand how calcium contributes to cell growth and disorders, including aging-related cardiac disease, diabetes, lysosomal cell dysfunction and the metastasis of cells in cancer.”
According to the researchers, the mechanism for how NAADP triggers the release of calcium, as well as the specific sites of calcium store targeted for release, were previously unknown. These findings indicate that NAADP, through its interaction with TPC2, targets a specific store of calcium in lysosomes, a specialized subunit within the cell that contain digestion enzymes and regulate cell function.
The study was a collaboration of investigative teams at four universities, including the laboratory of Dr. Michael Zhu at the Ohio State University, the laboratory of Dr. A. Mark Evans at the University of Edinburgh and the laboratory of Dr. Antony Galione at the University of Oxford.
The research was supported by grants from the United Kingdom's Wellcome Trust and the British Heart Foundation, the United States' National Institutes of Health, and the American Heart Association.