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Jaslan, Dawid; Ferro, Irene Flavia; Kudrina, Veronika; Yuan, Yu; Patel, Sandip and Grimm, Christian (2022): PI(3,5)P2 and NAADP: Team players or lone warriors?-New insights into TPC activation modes. In: Cell Calcium, Vol. 109, 102675

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Abstract

NAADP (nicotinic acid adenine dinucleotide phosphate) is a second messenger, releasing Ca2+ from acidic calcium stores such as endosomes and lysosomes. PI(3,5)P2 (phosphatidylinositol 3,5-bisphosphate) is a phosphoinositide, residing on endolysosomal membranes and likewise releasing Ca2+ from endosomes and lysosomes. Both compounds have been shown to activate endolysosomal two-pore channels (TPCs) in mammalian cells. However, their effects on ion permeability as demonstrated specifically for TPC2 differ. While PI(3,5)P2 elicits predominantly Na+-selective currents, NAADP increases the Ca2+ permeability of the channel. What happens when both compounds are applied simultaneously was unclear until recently

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