Crosstalk between TPC2 and IP(3)R regulates Ca(2+) signals.

Calcium (Ca2+) plays a pivotal role in cellular signal transmission by triggering downstream signaling in response to an increase in the cytosolic Ca2+ concentration. Intracellular organelles serve as Ca2+ stores that induce differently shaped Ca2+ signals. We discuss a study by Yuan et al. that investigated the interplay between the lysosomal two-pore channel 2 (TPC2) and endoplasmic reticulum (ER)-localized inositol 1,4,5-trisphosphate receptors (IP3Rs).

Humer C ，Schindl R ，Sallinger M 《-》

Two-pore channel-2 and inositol trisphosphate receptors coordinate Ca(2+) signals between lysosomes and the endoplasmic reticulum.

Yuan Y ，Arige V ，Saito R ，Mu Q ，Brailoiu GC ，Pereira GJS ，Bolsover SR ，Keller M ，Bracher F ，Grimm C ，Brailoiu E ，Marchant JS ，Yule DI ，Patel S ... -  《Cell Reports》

Neighbourhood Watch: Two-pore-2 channels talking to IP3 receptors.

The recent elegant study by Y. Yuan and colleagues examined functional relationships between the lysosomal two-pore channels 2 (TPC2) and IP3 receptors (IP3Rs) located in the endoplasmic reticulum [1]. The findings of this study suggest functional coupling of these channels and receptors. The study also describes interesting novel phenomena, which may indicate an additional coupling mechanism.

Criddle DN ，Tepikin AV 《-》

IP(3) Receptors Preferentially Associate with ER-Lysosome Contact Sites and Selectively Deliver Ca(2+) to Lysosomes.

Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) allow extracellular stimuli to redistribute Ca2+ from the ER to cytosol or other organelles. We show, using small interfering RNA (siRNA) and vacuolar H+-ATPase (V-ATPase) inhibitors, that lysosomes sequester Ca2+ released by all IP3R subtypes, but not Ca2+ entering cells through store-operated Ca2+ entry (SOCE). A low-affinity Ca2+ sensor targeted to lysosomal membranes reports large, local increases in cytosolic [Ca2+] during IP3-evoked Ca2+ release, but not during SOCE. Most lysosomes associate with endoplasmic reticulum (ER) and dwell at regions populated by IP3R clusters, but IP3Rs do not assemble ER-lysosome contacts. Increasing lysosomal pH does not immediately prevent Ca2+ uptake, but it causes lysosomes to slowly redistribute and enlarge, reduces their association with IP3Rs, and disrupts Ca2+ exchange with ER. In a "piston-like" fashion, ER concentrates cytosolic Ca2+ and delivers it, through large-conductance IP3Rs, to a low-affinity lysosomal uptake system. The involvement of IP3Rs allows extracellular stimuli to regulate Ca2+ exchange between the ER and lysosomes.

Atakpa P ，Thillaiappan NB ，Mataragka S ，Prole DL ，Taylor CW ... -  《Cell Reports》

High-throughput analyses of IP3 receptor behavior.

Taylor CW ，Tovey SC ，Rossi AM 《-》