Margarida Ruas

TL;DR: It is shown that two-pore channels (TPCs) comprise a family of NAADP receptors, with human TPC1 and chicken TPCN3 being expressed on endosomal membranes, andhuman TPC2 on lysosome membranes when expressed in HEK293 cells, which will advance the understanding of the physiological role ofNAADP.

TL;DR: The findings illustrate the importance of PLCzeta during fertilization and suggest that mutant forms of P LCzeta may underlie certain types of human male infertility.

TL;DR: This study shows that immunopurified endogenous TPC complexes possess the hallmark properties ascribed to NAADP receptors, including nanomolar ligand affinity, and proposes that NAadP regulates endolysosomal Ca2+ storage and release via TPCs and coordinates endoplasmic reticulum Ca2+.

TL;DR: It is shown that TPC2, the major lysosomal targeted isoform, is a cation channel with selectivity for Ca2+ that will enable it to act as a Ca 2+ release channel in the cellular environment, and provides a framework for understanding how NAADP can mediate key physiological events.

TL;DR: TPCs are established as Ca2+‐permeable channels indispensable for NAADP signalling, and high‐affinityNAADP binding still occurs in Tpcn1/2−/− tissue, suggesting that NAadP regulation is conferred by an accessory protein.