NAADP-binding proteins find their identity. Issue 3 (March 2022)

• Record Type: Journal Article
• Authors: Marchant, Jonathan S.; Gunaratne, Gihan S.; Cai, Xinjiang; Slama, James T.; Patel, Sandip
• Is Part Of: Trends in biochemical sciences. Volume 47:Issue 3(2022)
• Page Start: 235
• Page End: 249
• Publication Date: 2022-03
• Subjects: calcium signaling -- endosomes -- lysosomes -- cancer -- photoaffinity probes; Biochemistry -- Periodicals; 572
• DOI: 10.1016/j.tibs.2021.10.008
• Languages: English
• ISSNs: 0968-0004

Abstract

Abstract : Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca 2+ 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. Highlights: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca 2+ by activating ion channels known as two-pore channels (TPCs), resident on endosomes and lysosomes. The mechanism of TPC activation by NAADP is unclear as no binding site(s) for NAADP has been identified on the TPC complex. It has long been postulated that NAADP activates vertebrate TPCs indirectly via unidentified ~23-kDa NAADP-binding proteins (NAADP-BPs) associated with the TPC complex. Recent work has revealed the identity of these elusive NAADP-BPs as Jupiter microtubule associated homolog 2 (JPT2) and 'like-Sm' protein 12 (LSM12). These discoveries enable new insight into this signaling pathway and the role of NAADP in cellular physiology and disease.