Liquid liquid phase separation of the intrinsically disordered protein JPT2 compartmentalizes components of NAADP-evoked Ca²⁺ signaling.

ABSTRACT: Nicotinic acid adenine dinucleotide phosphate (NAADP) is a Ca²⁺-releasing second messenger that activates two-pore channels (TPCs) on endosomes and lysosomes. Rather than binding TPCs directly, NAADP acts through cytoplasmic NAADP-binding proteins (NAADP-BPs) which are essential for endolysosomal Ca²⁺ release. Here we characterized the properties of two recombinant, purified NAADP-BPs: Jupiter Microtubule Associated Homolog 2 (JPT2) and like-Sm protein 12 (LSM12). In contrast to LSM12, JPT2 is predicted to be an intrinsically disordered protein, a feature confirmed by circular dichroism and NMR spectroscopy. Under conditions of low Na⁺ concentration or molecular crowding, JPT2 underwent phase separation, as demonstrated by multiple orthogonal approaches. JP

SUBMITTER: Kumar S 

PROVIDER: S-EPMC12803092 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature