Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA.
Trends Biochem Sci. 2022 Mar;47(3):235-249. doi: 10.1016/j.tibs.2021.10.008. Epub 2021 Nov 20.
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca 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.
烟酰胺腺嘌呤二核苷酸磷酸 (NAADP) 是一种第二信使，通过激活称为双孔通道 (TPCs) 的离子通道从内体和溶酶体中释放 Ca。然而，尚未在 TPCs 上鉴定出 NAADP 结合位点。相反，NAADP 通过与构成 TPC 复合物一部分的 NAADP 结合蛋白 (NAADP-BP) 相互作用间接激活 TPCs。经过十年的研究，最近发现了两种不同的 NAADP-BP：木星微管相关同源物 2 (JPT2) 和类 Sm 蛋白 12 (LSM12)。这些发现弥合了 NAADP 产生和 TPCs 中 NAADP 激活之间的差距，为理解和操纵 NAADP 信号通路提供了新的机会。这些 NAADP-BP 的揭示将促进未来的研究，以确定 NAADP 作用的分子舞蹈。
