NAADP-binding proteins find their identity
2022
Marchant, Jonathan S. | Gunaratne, Gihan S. | Cai, Xinjiang | Slama, James T. | Patel, Sandip
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca²⁺ from endosomes and lysosomes by activating ion channels called two-pore channels (TPCs). However, no NAADP-binding site has been identified on TPCs. Rather, NAADP activates TPCs indirectly by engaging NAADP-binding proteins (NAADP-BPs) that form part of the TPC complex. After a decade of searching, two different NAADP-BPs were recently identified: Jupiter microtubule associated homolog 2 (JPT2) and like-Sm protein 12 (LSM12). These discoveries bridge the gap between NAADP generation and NAADP activation of TPCs, providing new opportunity to understand and manipulate the NAADP-signaling pathway. The unmasking of these NAADP-BPs will catalyze future studies to define the molecular choreography of NAADP action.
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