STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading

Article Article scientifique Article STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading eng 2025-03-21 2025-05-05 author Rabesahala de Meritens Camille 0000-0002-0380-6881 Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 948457 author Carreras Sureda Amado 0000-0002-9032-5639 Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 918518 Département de physiologie cellulaire et métabolisme (PHYME) author Rosa Nicolas 0000-0003-4902-177X Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 403591 Département de physiologie cellulaire et métabolisme (PHYME) author Pick Robert 0000-0001-9785-8481 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 921203 Département de pathologie et immunologie (PATIM) author Scheiermann Christoph 0000-0002-9212-0995 Department of Pathology and Immunology, University of Geneva, Geneva, Switzerland. 891044 Département de pathologie et immunologie (PATIM) author Demaurex Nicolas 0000-0002-9933-6772 Department of Cell Physiology and Metabolism, University of Geneva, Geneva, Switzerland. 24642 Département de physiologie cellulaire et métabolisme (PHYME) e202406053 10.1083/jcb.202406053 40116769 0021-9525 PMC11927589 https://rupress.org/jcb/article/224/5/e202406053/277339/STIM1-2-maintain-signaling-competence-at-ER-PM Neutrophils are highly motile leukocytes that migrate inside tissues to destroy invading pathogens. Ca2+ signals coordinate leukocytes migration, but whether Ca2+ fluxes mediated by Stim proteins at ER-PM contact sites regulate neutrophil actin-based motility is unclear. Here, we show that myeloid-specific Stim1/2 ablation decreases basal cytosolic Ca2+ levels and prevents adhesion-induced Ca2+ elevations in mouse neutrophils, reducing actin fiber formation and impairing spreading. Unexpectedly, more ER-PM contact sites were detected on the actin-poor adhesive membranes of Stim1/2-deficient neutrophils, which had reduced inositol-1,4,5-trisphosphate receptor (IP3R) immunoreactivity on confocal and immunogold micrographs despite preserved IP3R levels on western blots. Remarkably, Stim1/2-deficient neutrophils regained signaling and spreading competence in Ca2+-rich solutions and were recruited more effectively in mouse inflamed cremaster muscles in vivo. Our findings indicate that Stim1/2 preserve IP3R functionality in neutrophils, generating adhesion-dependent Ca2+ signals that control actin dynamics during neutrophil spreading. Stim proteins thus maintain IP3R signaling competence at adhesive membranes, enabling Ca2+-dependent actin remodeling during spreading in mouse neutrophils. Animals Stromal Interaction Molecule 1 / metabolism Stromal Interaction Molecule 1 / genetics Neutrophils / metabolism Endoplasmic Reticulum / metabolism Stromal Interaction Molecule 2 / metabolism Stromal Interaction Molecule 2 / genetics Mice Calcium Signaling Calcium / metabolism Inositol 1,4,5-Trisphosphate Receptors / metabolism Inositol 1,4,5-Trisphosphate Receptors / genetics Mice, Inbred C57BL Mice, Knockout Actins / metabolism Signal Transduction Cell Adhesion Membrane Glycoproteins / metabolism Membrane Glycoproteins / genetics Cell Movement Cell Membrane / metabolism Dewey 612 Dewey 616.07 Swiss National Science Foundation Calcium signaling at membrane contact sites during phagocytosis 189042 CH Projects Swiss National Science Foundation Development of CaMP-AID, a novel method to improve ion channel drug safety and efficacy 221284 CH Projects 134 Département de physiologie cellulaire et métabolisme 21C 137 Département de pathologie et immunologie 21F false 168 Signaux intracellulaires 210 1259 L'influence du rôle du cycle circadien sur l'immunité 995 The Journal of cell biology 224 5 ac037617-a462-463d-8793-45cd0fd108a1 Article (Published version) Public jcb_202406053.pdf 8735211 application/pdf CC BY-4.0 fcad84f1557a39dcde5c715d64730b9351d7dc0e72c9fa3be69856d7ee60010f fe4bb69a-3aca-48db-9254-f807c336f6e0 Supplemental data Public jcb_202406053_sourcedataf6.pdf 5396310 application/pdf cd77e606337608e7cd5893a268f31f45bfaaf5c994df5d9fe433b72b0a7e8047 f81d7e14-d080-4ee6-a6af-4941b58c9319 Supplemental data Public jcb_202406053_tables1-1.docx 58960 application/vnd.openxmlformats-officedocument.wordprocessingml.document 1267d64c3d79b4502ce1674afe453961ff32074800b3597d8338dbb3adcfa38c openAccess Faculté de médecine / Section de médecine fondamentale / Département de physiologie cellulaire et métabolisme Faculté de médecine / Section de médecine fondamentale / Département de pathologie et immunologie

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STIM1/2 maintain signaling competence at ER-PM contact sites during neutrophil spreading	The Journal of cell biology			2025	126	200

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