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1. Ca ²⁺ release or Ca ²⁺ entry, that is the question: what governs Ca ²⁺ oscillations in pancreatic β cells?

   https://doi.org/10.1152/ajpendo.00030.2023  

   Fletcher, Patrick A.; Thompson, Ben; Liu, Chanté; Bertram, Richard; Satin, Leslie S.; Sherman, Arthur S. (June 2023, American Journal of Physiology-Endocrinology and Metabolism)

   The standard model for Ca 2+ oscillations in insulin-secreting pancreatic β cells centers on Ca 2+ entry through voltage-activated Ca 2+ channels. These work in combination with ATP-dependent K + channels, which are the bridge between the metabolic state of the cells and plasma membrane potential. This partnership underlies the ability of the β cells to secrete insulin appropriately on a minute-to-minute time scale to control whole body plasma glucose. Though this model, developed over more than 40 years through many cycles of experimentation and mathematical modeling, has been very successful, it has been challenged by a hypothesis that calcium-induced calcium release from the endoplasmic reticulum through ryanodine or inositol trisphosphate (IP3) receptors is instead the key driver of islet oscillations. We show here that the alternative model is in fact incompatible with a large body of established experimental data and that the new observations offered in support of it can be better explained by the standard model. 

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2. Phosphatidylinositol 3, 5‐bisphosphate regulates Ca ²⁺ transport during yeast vacuolar fusion through the Ca ²⁺ ATPase Pmc1

   https://doi.org/10.1111/tra.12736  

   Miner, Gregory E.; Sullivan, Katherine D.; Zhang, Chi; Rivera‐Kohr, David; Guo, Annie; Hurst, Logan R.; Ellis, Ez C.; Starr, Matthew L.; Jones, Brandon C.; Fratti, Rutilio A. (June 2020, Traffic)

   Abstract The transport of Ca²⁺across membranes precedes the fusion and fission of various lipid bilayers. Yeast vacuoles under hyperosmotic stress become fragmented through fission events that requires the release of Ca²⁺stores through the TRP channel Yvc1. This requires the phosphorylation of phosphatidylinositol‐3‐phosphate (PI3P) by the PI3P‐5‐kinase Fab1 to produce transient PI(3,5)P₂pools. Ca²⁺is also released during vacuole fusion upontrans‐SNARE complex assembly, however, its role remains unclear. The effect of PI(3,5)P₂on Ca²⁺flux during fusion was independent of Yvc1. Here, we show that while low levels of PI(3,5)P₂were required for Ca²⁺uptake into the vacuole, increased concentrations abolished Ca²⁺efflux. This was as shown by the addition of exogenous dioctanoyl PI(3,5)P₂or increased endogenous production of by the hyperactivefab1^T2250Amutant. In contrast, the lack of PI(3,5)P₂on vacuoles from the kinase deadfab1^EEEmutant showed delayed and decreased Ca²⁺uptake. The effects of PI(3,5)P₂were linked to the Ca²⁺pump Pmc1, as its deletion rendered vacuoles resistant to the effects of excess PI(3,5)P₂. Experiments with Verapamil inhibited Ca²⁺uptake when added at the start of the assay, while adding it after Ca²⁺had been taken up resulted in the rapid expulsion of Ca²⁺. Vacuoles lacking both Pmc1 and the H⁺/Ca²⁺exchanger Vcx1 lacked the ability to take up Ca²⁺and instead expelled it upon the addition of ATP. Together these data suggest that a balance of efflux and uptake compete during the fusion pathway and that the levels of PI(3,5)P₂can modulate which path predominates. 

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3. Phosphatidylserine affinity for and flip-flop dependence on Ca ²⁺ and Mg ²⁺ ions

   https://doi.org/10.1039/d4fd00206g  

   Hymas, Preston P; Conboy, John C (January 2025, Faraday Discussions)

   Ca²⁺ions are believed to play a crucial role in enzymatic regulation of lipid membrane asymmetry, yet direct effects of Ca²⁺on lipid flip-flop are unknown. Present work examines the influence of Ca–lipid interactions on lipid translocation. 

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4. Essential requirement for JPT2 in NAADP-evoked Ca ²⁺ signaling

   https://doi.org/10.1126/scisignal.abd5605  

   Gunaratne, Gihan S.; Brailoiu, Eugen; He, Shijun; Unterwald, Ellen M.; Patel, Sandip; Slama, James T.; Walseth, Timothy F.; Marchant, Jonathan S. (March 2021, Science Signaling)

   null (Ed.)

   Nicotinic acid adenine dinucleotide phosphate (NAADP) is a second messenger that releases Ca 2+ from acidic organelles through the activation of two-pore channels (TPCs) to regulate endolysosomal trafficking events. NAADP action is mediated by NAADP-binding protein(s) of unknown identity that confer NAADP sensitivity to TPCs. Here, we used a “clickable” NAADP-based photoprobe to isolate human NAADP-binding proteins and identified Jupiter microtubule-associated homolog 2 (JPT2) as a TPC accessory protein required for endogenous NAADP-evoked Ca 2+ signaling. JPT2 was also required for the translocation of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pseudovirus through the endolysosomal system. Thus, JPT2 is a component of the NAADP receptor complex that is essential for TPC-dependent Ca 2+ signaling and control of coronaviral entry. 

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5. Marine and Anthropogenic Bromopyrroles Alter Cellular Ca ²⁺ Dynamics of Murine Cortical Neuronal Networks by Targeting the Ryanodine Receptor and Sarco/Endoplasmic Reticulum Ca ²⁺ -ATPase

   https://doi.org/10.1021/acs.est.1c05214  

   Zheng, Jing; Antrobus, Shane; Feng, Wei; Purdy, Trevor N.; Moore, Bradley S.; Pessah, Isaac N. (December 2021, Environmental Science & Technology)