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PI4P STimulatING innate immune activation: beyond the Golgi

Cellular & Molecular Immunology volume 20, pages 1399–1400 (2023)Cite this article

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The cGAS–STING pathway is pivotal for sensing cytosolic DNA [2]. cGAS, a cytoplasmic DNA sensor, can be stimulated by DNA, and it consumes ATP and GTP to synthesize a second messenger, 2'3'-cGAMP, which binds to STING, resulting in STING conformational change, oligomerization, and activation; ultimately, this process leads to the production of cytokines such as type I interferon to mediate antiviral and antitumor immune responses (Fig. 1).

Phosphoinositides, derived from phosphatidylinositol (PI), are phospholipids in membranes and are also crucial signaling molecules [3]. The D-3, D-4, or D-5 positions in the inositol head group can be phosphorylated; therefore, a total of seven different PIP molecules exist in eukaryotes. Phosphatidylinositol 4-phosphate (PI4P) is distributed in various membrane components, with the highest amount in the trans-Golgi network (TGN) [4]. The PI4P level in cells is regulated by its PI4K synthetases (PI4KA, PI4KB, PI4K2A, and PI4K2B) and the lipid phosphatase SAC1. In addition to being a precursor for PIP2 and PIP3, PI4P is a crucial signaling molecule involved in vesicular transport, lipid transport, and organelle morphology maintenance.

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Fig. 1

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Acknowledgements

This work was supported by grants from the National Natural Science Foundation of China (Nos. 82271788, 81930039, and 32230033), the Future Scholar Program of Shandong University, and the Natural Science Foundation of Shandong Province (ZR2022YQ70).

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  1. These authors contributed equally: Yi Zheng, Xuejing Zhang.

Authors and Affiliations

  1. Key Laboratory of Infection and Immunity of Shandong Province and Department of Immunology, School of Basic Medical Sciences, Shandong University, Jinan, 250012, Shandong, China

    Yi Zheng, Xuejing Zhang & Chengjiang Gao

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  1. Yi Zheng
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YZ and XZ wrote the manuscript under the supervision of CG.

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Correspondence to Chengjiang Gao.

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Zheng, Y., Zhang, X. & Gao, C. PI4P STimulatING innate immune activation: beyond the Golgi. Cell Mol Immunol 20, 1399–1400 (2023). https://doi.org/10.1038/s41423-023-01044-7

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