What structures did, and did not, reveal about the function of the epithelial Ca2+ channels TRPV5 and TRPV6

Flores-Aldama, 2020, Evolutionary analyses reveal independent origins of gene repertoires and structural motifs associated to fast inactivation in calcium-selective TRPV channels, Sci Rep, 10, 8684, 10.1038/s41598-020-65679-6

Hoenderop, 2005, Calcium absorption across epithelia, Physiol Rev, 85, 373, 10.1152/physrev.00003.2004

Balzer, 2021, How Many Cell Types Are in the Kidney and What Do They Do?, Annu Rev Physiol, 84, 507, 10.1146/annurev-physiol-052521-121841

Peng, 2018, TRPV5 and TRPV6 Calcium-Selective Channels, 241

Hoenderop, 2003, Renal Ca2+ wasting, hyperabsorption, and reduced bone thickness in mice lacking TRPV5, J Clin Invest, 112, 1906, 10.1172/JCI200319826

Oddsson, 2015, Common and rare variants associated with kidney stones and biochemical traits, Nat Commun, 6, 7975, 10.1038/ncomms8975

Na, 2014, TRPV5: a Ca(2+) channel for the fine-tuning of Ca(2+) reabsorption, Handb Exp Pharmacol, 222, 321, 10.1007/978-3-642-54215-2_13

van Goor, 2017, TRP channels in calcium homeostasis: from hormonal control to structure-function relationship of TRPV5 and TRPV6, Biochim Biophys Acta Mol Cell Res, 1864, 883, 10.1016/j.bbamcr.2016.11.027

Voets, 2001, CaT1 and the calcium release-activated calcium channel manifest distinct pore properties, J Biol Chem, 276, 47767, 10.1074/jbc.C100607200

Yue, 2001, CaT1 manifests the pore properties of the calcium-release-activated calcium channel, Nature, 410, 705, 10.1038/35070596

Fecher-Trost, 2014, TRPV6 channels, Handb Exp Pharmacol, 222, 359, 10.1007/978-3-642-54215-2_14

Bianco, 2007, Marked disturbance of calcium homeostasis in mice with targeted disruption of the Trpv6 calcium channel gene, J Bone Miner Res, 22, 274, 10.1359/jbmr.061110

Benn, 2008, Active intestinal calcium transport in the absence of transient receptor potential vanilloid type 6 and calbindin-D9k, Endocrinology, 149, 3196, 10.1210/en.2007-1655

Kutuzova, 2008, TRPV6 is not required for 1alpha,25-dihydroxyvitamin D3-induced intestinal calcium absorption in vivo, Proc Natl Acad Sci U S A, 105, 19655, 10.1073/pnas.0810761105

Burren, 2018, TRPV6 compound heterozygous variants result in impaired placental calcium transport and severe undermineralization and dysplasia of the fetal skeleton, Am J Med Genet A, 176, 1950, 10.1002/ajmg.a.40484

Weissgerber, 2011, Male fertility depends on Ca(2)+ absorption by TRPV6 in epididymal epithelia, Sci Signal, 4, ra27, 10.1126/scisignal.2001791

Zou, 2020, TRPV6 variants confer susceptibility to chronic pancreatitis in the Chinese population, Hum Mutat, 41, 1351, 10.1002/humu.24032

Segerstolpe, 2016, Single-Cell Transcriptome Profiling of Human Pancreatic Islets in Health and Type 2 Diabetes, Cell Metab, 24, 593, 10.1016/j.cmet.2016.08.020

Zhuang, 2002, Calcium-selective ion channel, CaT1, is apically localized in gastrointestinal tract epithelia and is aberrantly expressed in human malignancies, Lab Invest, 82, 1755, 10.1097/01.LAB.0000043910.41414.E7

Sahin-Toth, 2020, Channelopathy of the Pancreas Causes Chronic Pancreatitis, Gastroenterology, 158, 1538, 10.1053/j.gastro.2020.03.027

Stewart, 2020, TRPV6 as A Target for Cancer Therapy, J Cancer, 11, 374, 10.7150/jca.31640

Simonin, 2015, Optimization of TRPV6 Calcium Channel Inhibitors Using a 3D Ligand-Based Virtual Screening Method, Angew Chem Int Ed Engl, 54, 14748, 10.1002/anie.201507320

Cunha, 2020, Natural product inspired optimization of a selective TRPV6 calcium channel inhibitor, RSC Med Chem, 11, 1032, 10.1039/D0MD00145G

Saotome, 2016, Crystal structure of the epithelial calcium channel TRPV6, Nature, 534, 506, 10.1038/nature17975

Liao, 2013, Structure of the TRPV1 ion channel determined by electron cryo-microscopy, Nature, 504, 107, 10.1038/nature12822

Singh, 2017, Swapping of transmembrane domains in the epithelial calcium channel TRPV6, Sci Rep, 7, 10669, 10.1038/s41598-017-10993-9

Hughes, 2018, Structural basis of TRPV5 channel inhibition by econazole revealed by cryo-EM, Nat Struct Mol Biol, 25, 53, 10.1038/s41594-017-0009-1

Lambers, 2006, Calbindin-D28K dynamically controls TRPV5-mediated Ca2+ transport, EMBO J, 25, 2978, 10.1038/sj.emboj.7601186

Cao, 2013, Interplay between calmodulin and phosphatidylinositol 4,5-bisphosphate in Ca2+-induced inactivation of transient receptor potential vanilloid 6 channels, J Biol Chem, 288, 5278, 10.1074/jbc.M112.409482

Niemeyer, 2001, Competitive regulation of CaT-like-mediated Ca2+ entry by protein kinase C and calmodulin, Proc Natl Acad Sci U S A, 98, 3600, 10.1073/pnas.051511398

Derler, 2006, Dynamic but not constitutive association of calmodulin with rat TRPV6 channels enables fine tuning of Ca2+-dependent inactivation, J Physiol, 577, 31, 10.1113/jphysiol.2006.118661

Thyagarajan, 2008, Hydrolysis of phosphatidylinositol 4,5-bisphosphate mediates calcium-induced inactivation of TRPV6 channels, J Biol Chem, 283, 14980, 10.1074/jbc.M704224200

de Groot, 2011, Molecular mechanisms of calmodulin action on TRPV5 and modulation by parathyroid hormone, Mol Cell Biol, 31, 2845, 10.1128/MCB.01319-10

Dang, 2019, Structural insight into TRPV5 channel function and modulation, Proc Natl Acad Sci U S A,, 116, 8869, 10.1073/pnas.1820323116

Hughes, 2018, Structural insights on TRPV5 gating by endogenous modulators, Nat Commun, 9, 4198, 10.1038/s41467-018-06753-6

Singh, 2018, Mechanism of calmodulin inactivation of the calcium-selective TRP channel TRPV6, Sci Adv, 4, eaau6088, 10.1126/sciadv.aau6088

Lambers, 2004, Regulation of the mouse epithelial Ca2(+) channel TRPV6 by the Ca(2+)-sensor calmodulin, J Biol Chem, 279, 28855, 10.1074/jbc.M313637200

Rohacs, 2005, PI(4,5)P2 regulates the activation and desensitization of TRPM8 channels through the TRP domain, Nat Neurosci, 8, 626, 10.1038/nn1451

Lee, 2005, PIP2 activates TRPV5 and releases its inhibition by intracellular Mg2+, J Gen Physiol, 126, 439, 10.1085/jgp.200509314

Yudin, 2021, Methods to study phosphoinositide regulation of ion channels, Methods Enzymol, 652, 49, 10.1016/bs.mie.2021.01.025

Zakharian, 2011, Intracellular ATP supports TRPV6 activity via lipid kinases and the generation of PtdIns(4,5) P(2), FASEB J, 25, 3915, 10.1096/fj.11-184630

Velisetty, 2016, A molecular determinant of phosphoinositide affinity in mammalian TRPV channels, Sci Rep, 6, 27652, 10.1038/srep27652

Hughes, 2019, Structure-based characterization of novel TRPV5 inhibitors, Elife, 8, 10.7554/eLife.49572

Thyagarajan, 2009, Phospholipase C-mediated regulation of transient receptor potential vanilloid 6 channels: implications in active intestinal Ca2+ transport, Mol Pharmacol, 75, 608, 10.1124/mol.108.052449

Fluck, 2022, Structural basis of TRPV5 regulation by physiological and pathophysiological modulators, Cell Reports, 39, 110737, 10.1016/j.celrep.2022.110737

McGoldrick, 2018, Opening of the human epithelial calcium channel TRPV6, Nature, 553, 233, 10.1038/nature25182

Bhardwaj, 2020, Inactivation-mimicking block of the epithelial calcium channel TRPV6, Sci Adv, 6, 10.1126/sciadv.abe1508

Cai, 2021, Auto-inhibitory intramolecular S5/S6 interaction in the TRPV6 channel regulates breast cancer cell migration and invasion, Commun Biol, 4, 990, 10.1038/s42003-021-02521-3

Nishida, 2007, Crystal structure of a Kir3.1-prokaryotic Kir channel chimera, EMBO J, 26, 4005, 10.1038/sj.emboj.7601828

Yin, 2019, Structural basis of cooling agent and lipid sensing by the cold-activated TRPM8 channel, Science, 363, 10.1126/science.aav9334

Liu, 2020, Regulation of the cold-sensing TRPM8 channels by phosphoinositides and Gq-coupled receptors, Channels (Austin), 14, 79, 10.1080/19336950.2020.1734266

Fecher-Trost, 2013, The in vivo TRPV6 protein starts at a non-AUG triplet, decoded as methionine, upstream of canonical initiation at AUG, J Biol Chem, 288, 16629, 10.1074/jbc.M113.469726

Nilius, 2001, Pharmacological modulation of monovalent cation currents through the epithelial Ca2+ channel ECaC1, Br J Pharmacol, 134, 453, 10.1038/sj.bjp.0704272

Neuberger, 2021, Structural mechanisms of TRPV6 inhibition by ruthenium red and econazole, Nat Commun, 12, 6284, 10.1038/s41467-021-26608-x

Landowski, 2011, Chemical inhibitors of the calcium entry channel TRPV6, Pharm Res, 28, 322, 10.1007/s11095-010-0249-9

Hofer, 2013, Design, synthesis and pharmacological characterization of analogs of 2-aminoethyl diphenylborinate (2-APB), a known store-operated calcium channel blocker, for inhibition of TRPV6-mediated calcium transport, Bioorg Med Chem, 21, 3202, 10.1016/j.bmc.2013.03.037

Singh, 2018, Structural bases of TRP channel TRPV6 allosteric modulation by 2-APB, Nat Commun, 9, 2465, 10.1038/s41467-018-04828-y