Research reveals PLCγ2 regulates calcium oscillation and chemoattractant response in neutrophil-like cells, suggesting its role in chemotaxis regulation.
The relationship between calcium oscillation and cell sensitivity is poorly understood. Calcium oscillation can occur spontaneously or be triggered upon receptor-ligand 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 (IP 3 ). Here, we show that neutrophil-like HL60 cells lacking PLCγ2 ( 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 PI 3 Kγ activation and actin polymerization. Notably, plcg2 kd cells display increased sensitivity and can respond to chemoattractant gradients at a subsensitive concentrations. 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.
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Xu et al. (2025) studied this question.