Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells
Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced lysosomal Ca2+ release may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced...
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Frontiers Media S.A.
2022-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2022.874043/full |
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| author | Pawan Faris Claudio Casali Sharon Negri Lara Iengo Marco Biggiogera Angela Serena Maione Francesco Moccia |
| author_facet | Pawan Faris Claudio Casali Sharon Negri Lara Iengo Marco Biggiogera Angela Serena Maione Francesco Moccia |
| author_sort | Pawan Faris |
| collection | DOAJ |
| description | Nicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced lysosomal Ca2+ release may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release (CICR) mechanism. NAADP-induced intracellular Ca2+ signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca2+ release resulted in the Ca2+-dependent recruitment of ER-embedded InsP3Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca2+ to recruit ER-embedded InsP3Rs through CICR. NAADP-induced EL Ca2+ mobilization via EL TPC was found to trigger the intracellular Ca2+ signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca2+ release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders. |
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| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-13T09:33:57Z |
| publishDate | 2022-03-01 |
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| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-ad2eee8d4aa041fbb6e8f0a148f53aa02022-12-21T23:52:25ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2022-03-011010.3389/fcell.2022.874043874043Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal CellsPawan Faris0Claudio Casali1Sharon Negri2Lara Iengo3Marco Biggiogera4Angela Serena Maione5Francesco Moccia6Laboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Pavia, ItalyLaboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Pavia, ItalyLaboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Pavia, ItalyVascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino, IRCCS, Milan, ItalyLaboratory of Cell Biology and Neurobiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Pavia, ItalyVascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino, IRCCS, Milan, ItalyLaboratory of General Physiology, Department of Biology and Biotechnology “Lazzaro Spallanzani”, University of Pavia, Pavia, ItalyNicotinic acid adenine dinucleotide phosphate (NAADP) is a newly discovered second messenger that gates two pore channels 1 (TPC1) and 2 (TPC2) to elicit endo-lysosomal (EL) Ca2+ release. NAADP-induced lysosomal Ca2+ release may be amplified by the endoplasmic reticulum (ER) through the Ca2+-induced Ca2+ release (CICR) mechanism. NAADP-induced intracellular Ca2+ signals were shown to modulate a growing number of functions in the cardiovascular system, but their occurrence and role in cardiac mesenchymal stromal cells (C-MSCs) is still unknown. Herein, we found that exogenous delivery of NAADP-AM induced a robust Ca2+ signal that was abolished by disrupting the lysosomal Ca2+ store with Gly-Phe β-naphthylamide, nigericin, and bafilomycin A1, and blocking TPC1 and TPC2, that are both expressed at protein level in C-MSCs. Furthermore, NAADP-induced EL Ca2+ release resulted in the Ca2+-dependent recruitment of ER-embedded InsP3Rs and SOCE activation. Transmission electron microscopy revealed clearly visible membrane contact sites between lysosome and ER membranes, which are predicted to provide the sub-cellular framework for lysosomal Ca2+ to recruit ER-embedded InsP3Rs through CICR. NAADP-induced EL Ca2+ mobilization via EL TPC was found to trigger the intracellular Ca2+ signals whereby Fetal Bovine Serum (FBS) induces C-MSC proliferation. Furthermore, NAADP-evoked Ca2+ release was required to mediate FBS-induced extracellular signal-regulated kinase (ERK), but not Akt, phosphorylation in C-MSCs. These finding support the notion that NAADP-induced TPC activation could be targeted to boost proliferation in C-MSCs and pave the way for future studies assessing whether aberrant NAADP signaling in C-MSCs could be involved in cardiac disorders.https://www.frontiersin.org/articles/10.3389/fcell.2022.874043/fullnicotinic acid adenine dinucleotide phosphate (NAADP)two-pore channels (TPCs)membrane contact sitesstore operated Ca2+ entrycardiac mesenchymal stem cellsproliferation |
| spellingShingle | Pawan Faris Claudio Casali Sharon Negri Lara Iengo Marco Biggiogera Angela Serena Maione Francesco Moccia Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells Frontiers in Cell and Developmental Biology nicotinic acid adenine dinucleotide phosphate (NAADP) two-pore channels (TPCs) membrane contact sites store operated Ca2+ entry cardiac mesenchymal stem cells proliferation |
| title | Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells |
| title_full | Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells |
| title_fullStr | Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells |
| title_full_unstemmed | Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells |
| title_short | Nicotinic Acid Adenine Dinucleotide Phosphate Induces Intracellular Ca2+ Signalling and Stimulates Proliferation in Human Cardiac Mesenchymal Stromal Cells |
| title_sort | nicotinic acid adenine dinucleotide phosphate induces intracellular ca2 signalling and stimulates proliferation in human cardiac mesenchymal stromal cells |
| topic | nicotinic acid adenine dinucleotide phosphate (NAADP) two-pore channels (TPCs) membrane contact sites store operated Ca2+ entry cardiac mesenchymal stem cells proliferation |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2022.874043/full |
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