{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,19]],"date-time":"2025-06-19T05:54:41Z","timestamp":1750312481961,"version":"3.33.0"},"reference-count":105,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T00:00:00Z","timestamp":1737936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"German Research Council","award":["GE514\/6-3"],"award-info":[{"award-number":["GE514\/6-3"]}]},{"name":"German Research Council","award":["SFB 1009-A6"],"award-info":[{"award-number":["SFB 1009-A6"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Weibel-Palade bodies (WPB) are secretory organelles exclusively found in endothelial cells and among other cargo proteins, contain the hemostatic von-Willebrand factor (VWF). Stimulation of endothelial cells results in exocytosis of WPB and release of their cargo into the vascular lumen, where VWF unfurls into long strings of up to 1000 \u00b5m and recruits platelets to sites of vascular injury, thereby mediating a crucial step in the hemostatic response. The function of VWF is strongly correlated to its structure; in order to fulfill its task in the vascular lumen, VWF has to undergo a complex packing\/processing after translation into the ER. ER, Golgi and WPB themselves provide a unique milieu for the maturation of VWF, which at the level of the Golgi consists of a low pH and elevated Ca<jats:sup>2+<\/jats:sup> concentrations. WPB are also characterized by low luminal pH, but their Ca<jats:sup>2+<\/jats:sup> content has not been addressed so far. Here, we employed a chemigenetic approach to circumvent the problems of Ca<jats:sup>2+<\/jats:sup> imaging in an acidic environment and show that WPB indeed also harbor elevated Ca<jats:sup>2+<\/jats:sup> concentrations. We also show that depletion of the Golgi resident Ca<jats:sup>2+<\/jats:sup> pump ATP2C1 resulted in only a minor decrease of luminal Ca<jats:sup>2+<\/jats:sup> in WPB suggesting additional mechanisms for Ca<jats:sup>2+<\/jats:sup> uptake into the organelle.<\/jats:p>","DOI":"10.1371\/journal.pone.0316854","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T18:39:32Z","timestamp":1738003172000},"page":"e0316854","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemigenetic Ca2+ indicators report elevated Ca2+ levels in endothelial Weibel-Palade bodies"],"prefix":"10.1371","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-8000-5831","authenticated-orcid":true,"given":"Julian","family":"Terglane","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Mertes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7292-8308","authenticated-orcid":true,"given":"Sarah","family":"Weischer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2101-8416","authenticated-orcid":true,"given":"Thomas","family":"Zobel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kai","family":"Johnsson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-8206","authenticated-orcid":true,"given":"Volker","family":"Gerke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,1,27]]},"reference":[{"issue":"5","key":"pone.0316854.ref001","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1182\/blood.V73.5.1109.1109","article-title":"PADGEM (GMP140) is a component of Weibel-Palade bodies of human endothelial cells","volume":"73","author":"R Bonfanti","year":"1989","journal-title":"Blood"},{"issue":"11","key":"pone.0316854.ref002","doi-asserted-by":"crossref","first-page":"4150","DOI":"10.1182\/blood-2003-10-3685","article-title":"The Tie-2 ligand angiopoietin-2 is stored in and rapidly released upon stimulation from endothelial cell Weibel-Palade bodies","volume":"103","author":"U Fiedler","year":"2004","journal-title":"Blood"},{"issue":"Pt 19","key":"pone.0316854.ref003","doi-asserted-by":"crossref","first-page":"3939","DOI":"10.1242\/jcs.00711","article-title":"Weibel-Palade bodies recruit Rab27 by a content-driven, maturation-dependent mechanism that is independent of cell type","volume":"116","author":"MJ Hannah","year":"2003","journal-title":"J Cell Sci"},{"issue":"6","key":"pone.0316854.ref004","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1111\/j.1600-0854.2006.00415.x","article-title":"P-selectin and CD63 use different mechanisms for delivery to Weibel-Palade bodies","volume":"7","author":"KJ Harrison-Lavoie","year":"2006","journal-title":"Traffic Cph Den"},{"issue":"15","key":"pone.0316854.ref005","doi-asserted-by":"crossref","first-page":"2982","DOI":"10.1038\/sj.emboj.7600319","article-title":"Rab3D and annexin A2 play a role in regulated secretion of vWF, but not tPA, from endothelial cells","volume":"23","author":"M Knop","year":"2004","journal-title":"EMBO J"},{"issue":"16","key":"pone.0316854.ref006","first-page":"e2306624","article-title":"Evoked Weibel-Palade Body Exocytosis Modifies the Endothelial Cell Surface by Releasing a Substrate-Selective Phosphodiesterase.","volume":"11","author":"J Na\u00df","year":"2024","journal-title":"Adv Sci Weinh Baden-Wurtt Ger"},{"issue":"2","key":"pone.0316854.ref007","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1182\/blood-2003-08-2891","article-title":"Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments","volume":"104","author":"I \u00d8ynebr\u00e5ten","year":"2004","journal-title":"Blood"},{"issue":"4","key":"pone.0316854.ref008","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1002\/ar.1092370407","article-title":"Immunoelectron microscopy on the localization of endothelin in the umbilical vein of perinatal rabbits","volume":"237","author":"Y Sakamoto","year":"1993","journal-title":"Anat Rec"},{"issue":"4","key":"pone.0316854.ref009","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1182\/blood.V82.4.1184.1184","article-title":"CD63 is a component of Weibel-Palade bodies of human endothelial cells","volume":"82","author":"UM Vischer","year":"1993","journal-title":"Blood"},{"issue":"1","key":"pone.0316854.ref010","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1083\/jcb.95.1.355","article-title":"Immunolocalization of von Willebrand protein in Weibel-Palade bodies of human endothelial cells","volume":"95","author":"DD Wagner","year":"1982","journal-title":"J Cell Biol"},{"issue":"1","key":"pone.0316854.ref011","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1083\/jcb.23.1.101","article-title":"NEW CYTOPLASMIC COMPONENTS IN ARTERIAL ENDOTHELIA","volume":"23","author":"ER Weibel","year":"1964","journal-title":"J Cell Biol"},{"issue":"9","key":"pone.0316854.ref012","doi-asserted-by":"crossref","first-page":"1757","DOI":"10.1084\/jem.188.9.1757","article-title":"Endothelial cell \u201cmemory\u201d of inflammatory stimulation: human venular endothelial cells store interleukin 8 in Weibel-Palade bodies.","volume":"188","author":"B Wolff","year":"1998","journal-title":"J Exp Med"},{"key":"pone.0316854.ref013","doi-asserted-by":"crossref","first-page":"e71526","DOI":"10.7554\/eLife.71526","article-title":"V-ATPase V0a1 promotes Weibel-Palade body biogenesis through the regulation of membrane fission.","volume":"10","author":"Y Yamazaki","year":"2021","journal-title":"eLife"},{"issue":"2","key":"pone.0316854.ref014","doi-asserted-by":"crossref","first-page":"714","DOI":"10.1002\/jcp.20354","article-title":"Osteoprotegerin (OPG) is localized to the Weibel-Palade bodies of human vascular endothelial cells and is physically associated with von Willebrand factor","volume":"204","author":"ACW Zannettino","year":"2005","journal-title":"J Cell Physiol"},{"key":"pone.0316854.ref015","doi-asserted-by":"crossref","first-page":"813995","DOI":"10.3389\/fcell.2021.813995","article-title":"Weibel Palade Bodies: Unique Secretory Organelles of Endothelial Cells that Control Blood Vessel Homeostasis.","volume":"9","author":"J Na\u00df","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"7","key":"pone.0316854.ref016","doi-asserted-by":"crossref","first-page":"4072","DOI":"10.1073\/pnas.061307098","article-title":"Defect in regulated secretion of P-selectin affects leukocyte recruitment in von Willebrand factor-deficient mice","volume":"98","author":"CV Denis","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"5","key":"pone.0316854.ref017","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1182\/blood.V96.5.1808","article-title":"von Willebrand factor storage and multimerization: 2 independent intracellular processes","volume":"96","author":"SL Haberichter","year":"2000","journal-title":"Blood"},{"issue":"1","key":"pone.0316854.ref018","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1182\/blood-2004-02-0464","article-title":"Re-establishment of VWF-dependent Weibel-Palade bodies in VWD endothelial cells","volume":"105","author":"SL Haberichter","year":"2005","journal-title":"Blood"},{"issue":"7","key":"pone.0316854.ref019","doi-asserted-by":"crossref","first-page":"2452","DOI":"10.1182\/blood-2003-02-0599","article-title":"Analysis of intracellular storage and regulated secretion of 3 von Willebrand disease-causing variants of von Willebrand factor","volume":"102","author":"G Michaux","year":"2003","journal-title":"Blood"},{"issue":"7","key":"pone.0316854.ref020","doi-asserted-by":"crossref","first-page":"1802","DOI":"10.1016\/j.jtha.2023.03.027","article-title":"von Willebrand factor binds to angiopoietin-2 within endothelial cells and after release from Weibel-Palade bodies","volume":"21","author":"G Mobayen","year":"2023","journal-title":"J Thromb Haemost JTH"},{"issue":"4","key":"pone.0316854.ref021","doi-asserted-by":"crossref","first-page":"718","DOI":"10.1002\/rth2.12242","article-title":"Alternative trafficking of Weibel-Palade body proteins in CRISPR\/Cas9-engineered von Willebrand factor-deficient blood outgrowth endothelial cells","volume":"3","author":"M Schillemans","year":"2019","journal-title":"Res Pract Thromb Haemost"},{"issue":"9","key":"pone.0316854.ref022","doi-asserted-by":"crossref","first-page":"1956","DOI":"10.1111\/j.1538-7836.2007.02681.x","article-title":"Characterization of the interaction between von Willebrand factor and osteoprotegerin","volume":"5","author":"S Shahbazi","year":"2007","journal-title":"J Thromb Haemost JTH"},{"issue":"7","key":"pone.0316854.ref023","doi-asserted-by":"crossref","first-page":"102204","DOI":"10.1016\/j.rpth.2023.102204","article-title":"Angiopoietin-2 binds to multiple interactive sites within von","volume":"7","author":"A Texier","year":"2023","journal-title":"Willebrand factor. Res Pract Thromb Haemost"},{"issue":"2","key":"pone.0316854.ref024","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1002\/j.1460-2075.1993.tb05709.x","article-title":"Biogenesis of von Willebrand factor-containing organelles in heterologous transfected CV-1 cells","volume":"12","author":"J Voorberg","year":"1993","journal-title":"EMBO J"},{"issue":"2","key":"pone.0316854.ref025","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1016\/0092-8674(91)90648-I","article-title":"Induction of specific storage organelles by von Willebrand factor propolypeptide","volume":"64","author":"DD Wagner","year":"1991","journal-title":"Cell"},{"issue":"11","key":"pone.0316854.ref026","doi-asserted-by":"crossref","first-page":"3971","DOI":"10.1182\/blood-2001-11-0060","article-title":"Ultralarge multimers of von Willebrand factor form spontaneous high-strength bonds with the platelet glycoprotein Ib-IX complex: studies using optical tweezers","volume":"99","author":"M Arya","year":"2002","journal-title":"Blood"},{"issue":"2","key":"pone.0316854.ref027","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1182\/blood-2012-07-442285","article-title":"Unwinding the von Willebrand factor strings puzzle","volume":"121","author":"K De Ceunynck","year":"2013","journal-title":"Blood"},{"issue":"2","key":"pone.0316854.ref028","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/j.devcel.2005.12.012","article-title":"The physiological function of von Willebrand\u2019s factor depends on its tubular storage in endothelial Weibel-Palade bodies","volume":"10","author":"G Michaux","year":"2006","journal-title":"Dev Cell"},{"issue":"8","key":"pone.0316854.ref029","doi-asserted-by":"crossref","first-page":"2939","DOI":"10.1182\/blood.V88.8.2939.bloodjournal8882939","article-title":"Shear-dependent changes in the three-dimensional structure of human von Willebrand factor","volume":"88","author":"CA Siedlecki","year":"1996","journal-title":"Blood"},{"issue":"1","key":"pone.0316854.ref030","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1083\/jcb.113.1.195","article-title":"Assembly and routing of von Willebrand factor variants: the requirements for disulfide-linked dimerization reside within the carboxy-terminal 151 amino acids","volume":"113","author":"J Voorberg","year":"1991","journal-title":"J Cell Biol"},{"issue":"3","key":"pone.0316854.ref031","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.devcel.2014.03.021","article-title":"A two-tier Golgi-based control of organelle size underpins the functional plasticity of endothelial cells","volume":"29","author":"F Ferraro","year":"2014","journal-title":"Dev Cell"},{"issue":"19","key":"pone.0316854.ref032","doi-asserted-by":"crossref","first-page":"4098","DOI":"10.1038\/emboj.2011.297","article-title":"A pH-regulated dimeric bouquet in the structure of von Willebrand factor","volume":"30","author":"YF Zhou","year":"2011","journal-title":"EMBO J"},{"issue":"2","key":"pone.0316854.ref033","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1073\/pnas.0710079105","article-title":"Assembly of Weibel-Palade body-like tubules from N-terminal domains of von Willebrand factor","volume":"105","author":"RH Huang","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Pt 12","key":"pone.0316854.ref034","doi-asserted-by":"crossref","first-page":"2117","DOI":"10.1242\/jcs.007781","article-title":"High-pressure freezing provides insights into Weibel-Palade body biogenesis","volume":"120","author":"HL Zenner","year":"2007","journal-title":"J Cell Sci"},{"issue":"12","key":"pone.0316854.ref035","doi-asserted-by":"crossref","first-page":"3536","DOI":"10.1182\/blood.V83.12.3536.3536","article-title":"von Willebrand factor proteolytic processing and multimerization precede the formation of Weibel-Palade bodies","volume":"83","author":"UM Vischer","year":"1994","journal-title":"Blood"},{"issue":"7","key":"pone.0316854.ref036","doi-asserted-by":"crossref","first-page":"1508","DOI":"10.1093\/emboj\/16.7.1508","article-title":"Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage","volume":"16","author":"ED Anderson","year":"1997","journal-title":"EMBO J"},{"issue":"23","key":"pone.0316854.ref037","doi-asserted-by":"crossref","first-page":"16396","DOI":"10.1016\/S0021-9258(18)42016-9","article-title":"Human furin is a calcium-dependent serine endoprotease that recognizes the sequence Arg-X-X-Arg and efficiently cleaves anthrax toxin protective antigen","volume":"267","author":"SS Molloy","year":"1992","journal-title":"J Biol Chem"},{"issue":"9","key":"pone.0316854.ref038","doi-asserted-by":"crossref","first-page":"2349","DOI":"10.1182\/blood.V79.9.2349.2349","article-title":"Preferred sequence requirements for cleavage of pro-von Willebrand factor by propeptide-processing enzymes","volume":"79","author":"A Rehemtulla","year":"1992","journal-title":"Blood"},{"issue":"41","key":"pone.0316854.ref039","doi-asserted-by":"crossref","first-page":"17407","DOI":"10.1073\/pnas.0902977106","article-title":"Structural organization of Weibel-Palade bodies revealed by cryo-EM of vitrified endothelial cells","volume":"106","author":"JA Berriman","year":"2009","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"Pt 19","key":"pone.0316854.ref040","doi-asserted-by":"crossref","first-page":"3927","DOI":"10.1242\/jcs.00672","article-title":"Interaction of the actin cytoskeleton with microtubules regulates secretory organelle movement near the plasma membrane in human endothelial cells","volume":"116","author":"JB Manneville","year":"2003","journal-title":"J Cell Sci"},{"issue":"10","key":"pone.0316854.ref041","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1111\/j.1600-0854.2011.01248.x","article-title":"Myosin Va acts in concert with Rab27a and MyRIP to regulate acute von-Willebrand factor release from endothelial cells","volume":"12","author":"I Rojo Pulido","year":"2011","journal-title":"Traffic Cph Den"},{"key":"pone.0316854.ref042","doi-asserted-by":"crossref","first-page":"743124","DOI":"10.3389\/fcell.2021.743124","article-title":"HPS6 Regulates the Biogenesis of Weibel-Palade Body in Endothelial Cells Through Trafficking v-ATPase to Its Limiting Membrane","volume":"9","author":"J Lu","year":"2021","journal-title":"Front Cell Dev Biol"},{"issue":"23","key":"pone.0316854.ref043","doi-asserted-by":"crossref","first-page":"13497","DOI":"10.1016\/S0021-9258(18)80024-2","article-title":"In vitro multimerization of von Willebrand factor is triggered by low pH. Importance of the propolypeptide and free sulfhydryls","volume":"264","author":"TN Mayadas","year":"1989","journal-title":"J Biol Chem"},{"issue":"6","key":"pone.0316854.ref044","doi-asserted-by":"crossref","first-page":"e0270299","DOI":"10.1371\/journal.pone.0270299","article-title":"Acidification of endothelial Weibel-Palade bodies is mediated by the vacuolar-type H+-ATPase.","volume":"17","author":"J Terglane","year":"2022","journal-title":"PloS One."},{"issue":"4","key":"pone.0316854.ref045","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1083\/jcb.102.4.1320","article-title":"Initial glycosylation and acidic pH in the Golgi apparatus are required for multimerization of von Willebrand factor","volume":"102","author":"DD Wagner","year":"1986","journal-title":"J Cell Biol"},{"issue":"17","key":"pone.0316854.ref046","doi-asserted-by":"crossref","first-page":"5198","DOI":"10.1182\/bloodadvances.2022006978","article-title":"A conformational transition of the D\u2019D3 domain primes von Willebrand factor for multimerization","volume":"6","author":"S Gruber","year":"2022","journal-title":"Blood Adv"},{"issue":"22","key":"pone.0316854.ref047","doi-asserted-by":"crossref","first-page":"3314","DOI":"10.1182\/blood.2021014729","article-title":"Structural basis of von Willebrand factor multimerization and tubular storage","volume":"139","author":"J Zeng","year":"2022","journal-title":"Blood"},{"issue":"Pt 1","key":"pone.0316854.ref048","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1113\/jphysiol.2007.132993","article-title":"Rate, extent and concentration dependence of histamine-evoked Weibel-Palade body exocytosis determined from individual fusion events in human endothelial cells","volume":"583","author":"M Erent","year":"2007","journal-title":"J Physiol"},{"issue":"5","key":"pone.0316854.ref049","doi-asserted-by":"crossref","first-page":"4553","DOI":"10.3390\/ijms24054553","article-title":"Altered Storage and Function of von Willebrand Factor in Human Cardiac Microvascular Endothelial Cells Isolated from Recipient Transplant Hearts","volume":"24","author":"A Meli","year":"2023","journal-title":"Int J Mol Sci"},{"issue":"20","key":"pone.0316854.ref050","doi-asserted-by":"crossref","first-page":"4769","DOI":"10.1182\/blood-2011-10-387548","article-title":"von Willebrand factor (VWF) propeptide binding to VWF D\u2019D3 domain attenuates platelet activation and adhesion","volume":"119","author":"SR Madabhushi","year":"2012","journal-title":"Blood"},{"issue":"3","key":"pone.0316854.ref051","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1042\/BJ20110949","article-title":"Molecular mechanisms of endolysosomal Ca2+ signalling in health and disease","volume":"439","author":"AJ Morgan","year":"2011","journal-title":"Biochem J"},{"issue":"5","key":"pone.0316854.ref052","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1007\/s00018-020-03688-4","article-title":"Insulin granule biogenesis and exocytosis","volume":"78","author":"M Omar-Hmeadi","year":"2021","journal-title":"Cell Mol Life Sci CMLS"},{"issue":"5","key":"pone.0316854.ref053","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.tcb.2010.02.003","article-title":"Acidic calcium stores open for business: expanding the potential for intracellular Ca2+ signaling","volume":"20","author":"S Patel","year":"2010","journal-title":"Trends Cell Biol"},{"issue":"12","key":"pone.0316854.ref054","doi-asserted-by":"crossref","first-page":"183318","DOI":"10.1016\/j.bbamem.2020.183318","article-title":"Membrane transport proteins in melanosomes: Regulation of ions for pigmentation","volume":"1862","author":"P Wiriyasermkul","year":"2020","journal-title":"Biochim Biophys Acta Biomembr"},{"issue":"20","key":"pone.0316854.ref055","doi-asserted-by":"crossref","first-page":"5622","DOI":"10.1073\/pnas.1600108113","article-title":"TPC2 controls pigmentation by regulating melanosome pH and size","volume":"113","author":"AL Ambrosio","year":"2016","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pone.0316854.ref056","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1042\/BST0381424","article-title":"NAADP as an intracellular messenger regulating lysosomal calcium-release channels","volume":"38","author":"A Galione","year":"2010","journal-title":"Biochem Soc Trans"},{"issue":"1","key":"pone.0316854.ref057","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1083\/jcb.200103145","article-title":"Dense core secretory vesicles revealed as a dynamic Ca(2+) store in neuroendocrine cells with a vesicle-associated membrane protein aequorin chimaera","volume":"155","author":"KJ Mitchell","year":"2001","journal-title":"J Cell Biol"},{"issue":"13","key":"pone.0316854.ref058","doi-asserted-by":"crossref","first-page":"11057","DOI":"10.1074\/jbc.M210257200","article-title":"Ryanodine receptor type I and nicotinic acid adenine dinucleotide phosphate receptors mediate Ca2+ release from insulin-containing vesicles in living pancreatic beta-cells (MIN6).","volume":"278","author":"KJ Mitchell","year":"2003","journal-title":"J Biol Chem"},{"issue":"4","key":"pone.0316854.ref059","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1054\/ceca.2000.0111","article-title":"Calcium uptake, release and ryanodine binding in melanosomes from retinal pigment epithelium","volume":"27","author":"R Salceda","year":"2000","journal-title":"Cell Calcium"},{"issue":"7","key":"pone.0316854.ref060","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1111\/j.1460-9568.2008.06440.x","article-title":"Calcium dynamics in bovine adrenal medulla chromaffin cell secretory granules","volume":"28","author":"J Santodomingo","year":"2008","journal-title":"Eur J Neurosci"},{"issue":"7","key":"pone.0316854.ref061","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1007\/s00018-011-0845-9","article-title":"Intracellular organelles in the saga of Ca2+ homeostasis: different molecules for different purposes","volume":"69","author":"E Zampese","year":"2012","journal-title":"Cell Mol Life Sci CMLS"},{"issue":"6","key":"pone.0316854.ref062","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1021\/cb800025k","article-title":"HaloTag: a novel protein labeling technology for cell imaging and protein analysis.","volume":"3","author":"GV Los","year":"2008","journal-title":"ACS Chem Biol"},{"issue":"15","key":"pone.0316854.ref063","doi-asserted-by":"crossref","first-page":"6928","DOI":"10.1021\/jacs.2c01465","article-title":"Fluorescent and Bioluminescent Calcium Indicators with Tuneable Colors and Affinities","volume":"144","author":"N Mertes","year":"2022","journal-title":"J Am Chem Soc"},{"issue":"Pt 3","key":"pone.0316854.ref064","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1242\/jcs.115.3.599","article-title":"pH-dependent regulation of lysosomal calcium in macrophages","volume":"115","author":"KA Christensen","year":"2002","journal-title":"J Cell Sci"},{"issue":"2","key":"pone.0316854.ref065","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0248-4900(92)90128-N","article-title":"The calcium loading of secretory granules. A possible key event in stimulus-secretion coupling","volume":"75","author":"G Nicaise","year":"1992","journal-title":"Biol Cell"},{"issue":"2","key":"pone.0316854.ref066","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/84397","article-title":"A high signal-to-noise Ca(2+) probe composed of a single green fluorescent protein","volume":"19","author":"J Nakai","year":"2001","journal-title":"Nat Biotechnol"},{"issue":"2","key":"pone.0316854.ref067","doi-asserted-by":"crossref","first-page":"e0170934","DOI":"10.1371\/journal.pone.0170934","article-title":"Deciphering the molecular mechanism responsible for GCaMP6m\u2019s Ca2+-dependent change in fluorescence.","volume":"12","author":"LM Barnett","year":"2017","journal-title":"PloS One."},{"issue":"7","key":"pone.0316854.ref068","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1038\/nmeth.3891","article-title":"Quantitative assessment of fluorescent proteins","volume":"13","author":"PJ Cranfill","year":"2016","journal-title":"Nat Methods"},{"issue":"3","key":"pone.0316854.ref069","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1016\/S0006-3495(98)77870-1","article-title":"Green fluorescent protein as a noninvasive intracellular pH indicator","volume":"74","author":"M Kneen","year":"1998","journal-title":"Biophys J"},{"issue":"5","key":"pone.0316854.ref070","doi-asserted-by":"crossref","first-page":"2782","DOI":"10.1016\/S0006-3495(97)78307-3","article-title":"Use of the green fluorescent protein and its mutants in quantitative fluorescence microscopy","volume":"73","author":"GH Patterson","year":"1997","journal-title":"Biophys J"},{"issue":"9","key":"pone.0316854.ref071","doi-asserted-by":"crossref","first-page":"1509","DOI":"10.1002\/pro.684","article-title":"Green fluorescent protein: a perspective","volume":"20","author":"SJ Remington","year":"2011","journal-title":"Protein Sci Publ Protein Soc"},{"issue":"6","key":"pone.0316854.ref072","doi-asserted-by":"crossref","first-page":"1548","DOI":"10.3390\/ijms19061548","article-title":"Fluorescent Proteins for Investigating Biological Events in Acidic Environments.","volume":"19","author":"H Shinoda","year":"2018","journal-title":"Int J Mol Sci"},{"issue":"6","key":"pone.0316854.ref073","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.bpj.2016.04.054","article-title":"Genetically Encoded Fluorescent Indicators for Organellar Calcium Imaging","volume":"111","author":"J Suzuki","year":"2016","journal-title":"Biophys J"},{"issue":"12","key":"pone.0316854.ref074","doi-asserted-by":"crossref","first-page":"e202300022","DOI":"10.1002\/cbic.202300022","article-title":"HaloTag-Based Reporters for Fluorescence Imaging and Biosensing.","volume":"24","author":"A Cook","year":"2023","journal-title":"Chembiochem Eur J Chem Biol"},{"key":"pone.0316854.ref075","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.conb.2018.01.003","article-title":"Synthetic and genetically encoded fluorescent neural activity indicators","volume":"50","author":"C Deo","year":"2018","journal-title":"Curr Opin Neurobiol"},{"issue":"10","key":"pone.0316854.ref076","doi-asserted-by":"crossref","first-page":"2284","DOI":"10.1016\/j.bbamcr.2014.03.010","article-title":"New red-fluorescent calcium indicators for optogenetics, photoactivation and multi-color imaging","volume":"1843","author":"M Oheim","year":"2014","journal-title":"Biochim Biophys Acta"},{"issue":"3","key":"pone.0316854.ref077","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.ymeth.2008.09.025","article-title":"Chemical calcium indicators.","volume":"46","author":"RM Paredes","year":"2008","journal-title":"Methods San Diego Calif"},{"issue":"12","key":"pone.0316854.ref078","doi-asserted-by":"crossref","first-page":"7877","DOI":"10.1073\/pnas.082243699","article-title":"A monomeric red fluorescent protein","volume":"99","author":"RE Campbell","year":"2002","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"12","key":"pone.0316854.ref079","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1016\/j.jgg.2016.09.007","article-title":"BLOC-2 subunit HPS6 deficiency affects the tubulation and secretion of von Willebrand factor from mouse endothelial cells","volume":"43","author":"J Ma","year":"2016","journal-title":"J Genet Genomics Yi Chuan Xue Bao"},{"issue":"3","key":"pone.0316854.ref080","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/BJ20141358","article-title":"Differential calcium handling by the cis and trans regions of the Golgi apparatus","volume":"466","author":"FJ Aulestia","year":"2015","journal-title":"Biochem J"},{"issue":"4","key":"pone.0316854.ref081","doi-asserted-by":"crossref","first-page":"688","DOI":"10.1046\/j.1523-1747.2003.12528.x","article-title":"Human keratinocyte ATP2C1 localizes to the Golgi and controls Golgi Ca2+ stores","volume":"121","author":"MJ Behne","year":"2003","journal-title":"J Invest Dermatol"},{"issue":"20","key":"pone.0316854.ref082","doi-asserted-by":"crossref","first-page":"9198","DOI":"10.1073\/pnas.1004702107","article-title":"Unique characteristics of Ca2+ homeostasis of the trans-Golgi compartment","volume":"107","author":"V Lissandron","year":"2010","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"10","key":"pone.0316854.ref083","doi-asserted-by":"crossref","first-page":"1315","DOI":"10.1111\/j.1600-0854.2010.01096.x","article-title":"The SPCA1 Ca2+ pump and intracellular membrane trafficking","volume":"11","author":"M Micaroni","year":"2010","journal-title":"Traffic Cph Den"},{"issue":"6","key":"pone.0316854.ref084","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1016\/j.ceca.2015.09.002","article-title":"A new low-Ca2+ affinity GAP indicator to monitor high Ca2+ in organelles by luminescence","volume":"58","author":"M Rodr\u00edguez-Prados","year":"2015","journal-title":"Cell Calcium"},{"issue":"12","key":"pone.0316854.ref085","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1182\/blood.2019000786","article-title":"Proximity proteomics of endothelial Weibel-Palade bodies identifies novel regulator of von Willebrand factor secretion","volume":"134","author":"A Holthenrich","year":"2019","journal-title":"Blood"},{"issue":"7","key":"pone.0316854.ref086","doi-asserted-by":"crossref","first-page":"1057","DOI":"10.1083\/jcb.201207180","article-title":"Cab45 is required for Ca(2+)-dependent secretory cargo sorting at the trans-Golgi network","volume":"199","author":"J von Blume","year":"2012","journal-title":"J Cell Biol"},{"key":"pone.0316854.ref087","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/bs.mcb.2014.10.031","article-title":"Imaging approaches to measuring lysosomal calcium","volume":"126","author":"AJ Morgan","year":"2015","journal-title":"Methods Cell Biol"},{"issue":"11","key":"pone.0316854.ref088","doi-asserted-by":"crossref","first-page":"2396","DOI":"10.1021\/bi00552a018","article-title":"New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures","volume":"19","author":"RY Tsien","year":"1980","journal-title":"Biochemistry"},{"issue":"2","key":"pone.0316854.ref089","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1007\/s00418-001-0368-9","article-title":"Biogenesis and exocytosis of Weibel-Palade bodies","volume":"117","author":"JA van Mourik","year":"2002","journal-title":"Histochem Cell Biol"},{"issue":"22","key":"pone.0316854.ref090","doi-asserted-by":"crossref","first-page":"3509","DOI":"10.1182\/blood-2014-10-608596","article-title":"Content delivery to newly forming Weibel-Palade bodies is facilitated by multiple connections with the Golgi apparatus","volume":"125","author":"MJ Mourik","year":"2015","journal-title":"Blood"},{"issue":"12","key":"pone.0316854.ref091","doi-asserted-by":"crossref","first-page":"113501","DOI":"10.1016\/j.celrep.2023.113501","article-title":"P-selectin-dependent leukocyte adhesion is governed by endolysosomal two-pore channel 2","volume":"42","author":"J Goretzko","year":"2023","journal-title":"Cell Rep"},{"issue":"5755","key":"pone.0316854.ref092","doi-asserted-by":"crossref","first-page":"1782","DOI":"10.1126\/science.1116238","article-title":"SLC24A5, a putative cation exchanger, affects pigmentation in zebrafish and humans","volume":"310","author":"RL Lamason","year":"2005","journal-title":"Science"},{"issue":"49","key":"pone.0316854.ref093","first-page":"51107","article-title":"A dynamic pool of calcium in catecholamine storage vesicles. Exploration in living cells by a novel vesicle-targeted chromogranin A-aequorin chimeric photoprotein","volume":"279","author":"NR Mahapatra","year":"2004","journal-title":"J Biol Chem"},{"key":"pone.0316854.ref094","article-title":"TMEM165 replenishes lysosomal Ca2+ stores, protects cells against Ca2+ overload, and mediates Ca2+-induced lysosomal H+ leakage [Internet].","author":"R Chen","year":"2024","journal-title":"bioRxiv"},{"issue":"7","key":"pone.0316854.ref095","doi-asserted-by":"crossref","first-page":"eadk2317","DOI":"10.1126\/sciadv.adk2317","article-title":"A mechanism of lysosomal calcium entry","volume":"10","author":"M Zajac","year":"2024","journal-title":"Sci Adv"},{"key":"pone.0316854.ref096","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/164_2023_640","article-title":"Lysosomal Ion Channels and Lysosome-Organelle Interactions","volume":"278","author":"W Cai","year":"2023","journal-title":"Handb Exp Pharmacol"},{"issue":"Pt 1","key":"pone.0316854.ref097","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1242\/jcs.118836","article-title":"Direct mobilisation of lysosomal Ca2+ triggers complex Ca2+ signals","volume":"126","author":"BS Kilpatrick","year":"2013","journal-title":"J Cell Sci"},{"issue":"4","key":"pone.0316854.ref098","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.ceca.2015.03.006","article-title":"Coupling acidic organelles with the ER through Ca2+ microdomains at membrane contact sites","volume":"58","author":"CJ Penny","year":"2015","journal-title":"Cell Calcium"},{"key":"pone.0316854.ref099","article-title":"Calcium flow at ER-TGN contact sites facilitates secretory cargo export","author":"BR Ramazanov","year":"2024","journal-title":"Mol Biol Cell"},{"key":"pone.0316854.ref100","doi-asserted-by":"crossref","first-page":"988014","DOI":"10.3389\/fcell.2022.988014","article-title":"ER-mitochondria contact sites; a multifaceted factory for Ca2+ signaling and lipid transport","volume":"10","author":"ML Sassano","year":"2022","journal-title":"Front Cell Dev Biol"},{"issue":"1","key":"pone.0316854.ref101","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1161\/ATVBAHA.123.319939","article-title":"Physical Contacts Between Mitochondria and WPBs Participate in WPB Maturation","volume":"44","author":"J Ma","year":"2024","journal-title":"Arterioscler Thromb Vasc Biol"},{"issue":"11","key":"pone.0316854.ref102","doi-asserted-by":"crossref","first-page":"5282","DOI":"10.1182\/blood-2007-09-113746","article-title":"Selective release of molecules from Weibel-Palade bodies during a lingering kiss","volume":"111","author":"V Babich","year":"2008","journal-title":"Blood"},{"issue":"24","key":"pone.0316854.ref103","doi-asserted-by":"crossref","first-page":"22827","DOI":"10.1074\/jbc.M412547200","article-title":"Differential kinetics of cell surface loss of von Willebrand factor and its propolypeptide after secretion from Weibel-Palade bodies in living human endothelial cells","volume":"280","author":"MJ Hannah","year":"2005","journal-title":"J Biol Chem"},{"issue":"7","key":"pone.0316854.ref104","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: an open-source platform for biological-image analysis","volume":"9","author":"J Schindelin","year":"2012","journal-title":"Nat Methods"},{"issue":"12","key":"pone.0316854.ref105","doi-asserted-by":"crossref","first-page":"1226","DOI":"10.1038\/s41592-019-0582-9","article-title":"ilastik: interactive machine learning for (bio)image analysis","volume":"16","author":"S Berg","year":"2019","journal-title":"Nat Methods"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316854","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T18:39:58Z","timestamp":1738003198000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0316854"}},"subtitle":[],"editor":[{"given":"Ludger","family":"Johannes","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,1,27]]},"references-count":105,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,1,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0316854","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,27]]}}}