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Updated: Sep 11, 2025

Imaging G-protein Coupled Receptor GPCR-mediated Signaling Events that Control Chemotaxis of Dictyostelium Discoideum
Published on: September 20, 2011
PLCγ2 controls neutrophil-like cell sensitivity through calcium oscillation and gates chemoattractant concentration
Xuehua Xu1, Woo Sung Kim1, Arthur Lee1
1Chemotaxis Signaling Section, Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD, United States.
Abstract:
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 [Ca2+] increase during calcium oscillation is initiated from Ca2+ 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 PLCγ2 (plcg2kd ) 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 PI3Kγ activation and actin polymerization. Notably, plcg2kd 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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