ORIGINAL RESEARCH article
Front. Immunol.
Sec. Molecular Innate Immunity
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1633390
PLCg2 Controls Neutrophil-like Cell Sensitivity through Calcium Oscillation and Gates Chemoattractant Concentration Range for Chemotaxis
Provisionally accepted
- National Institute of Allergy and Infectious Diseases (NIH), Bethesda, United States
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sensitivity is poorly understood. Calcium oscillation can occur spontaneously or be triggered upon receptorligand binding. The cytosolic [Ca 2+ ] increase during calcium oscillation is initiated from Ca 2+ release from the intracellular stores through the phospholipase C (PLC)-derived inositol 1,4,5-trisphosphate (IP3). Here, we show that neutrophil-like HL60 cells lacking PLC2 (plcg2 kd ) exhibit impaired spontaneous calcium oscillation and a diminished calcium response to chemoattractant stimulation. These defects result in reduced membrane targeting of RasGAP CAPRI (calcium-promoted Ras inactivator), and subsequent elevated Ras activations and enhanced downstream signaling, including PI3K activation and actin polymerization. Notably, plcg2 kd cells display increased sensitivity and can respond to chemoattractant gradients at a subsensitive chemoattraction. Taken together, our findings identify PLCγ2 as a key regulator of spontaneous and chemoattractant-induced calcium signaling and demonstrate its essential role in controlling cell sensitivity and chemoattractant concentration range for chemotaxis through CAPRI-dependent Ras signaling.
Keywords: Chemotaxis, Neutrophil sensitivity, G protein coupled receptor (GPCR), PLC gamma 2, calcium oscillation and calcium signaling, calcium promoted Ras inactivator (CAPRI)
Received: 22 May 2025; Accepted: 17 Jul 2025.
Copyright: © 2025 Xu, Kim, Lee and Jin. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Xuehua Xu, National Institute of Allergy and Infectious Diseases (NIH), Bethesda, United States
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