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INNATE IMMUNITY

Disturbance of cytoskeleton primes RIG-I-like receptors

Nature Reviews Immunology volume 22, pages 654–655 (2022)Cite this article

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Michaela Gack and colleagues have found that disturbance of the cell cytoskeleton is a necessary priming step for activation of the RIG-I-like receptors (RLRs) RIG-I and MDA5. They show that remodelling of the actin cytoskeleton, which commonly occurs during virus infection, drives relocation of a PPP1R12C phosphatase complex to RIG-I and MDA5, where it dephosphorylates the RLRs to enable their activation.

Previous work from the Gack laboratory had identified eight putative PP1 regulatory proteins; in the current study Acharya et al. used siRNA-mediated knockdown to determine if these proteins directly regulate RLRs. They found that silencing of PPP1R12C, but not the other candidate proteins, enhanced phosphorylation of RIG-I and MDA5 to a similar extent as PP1α/γ deletion, suggesting PPP1R12C supports the dephosphorylation of RLRs. In agreement with this, depletion of PPP1R12C impaired IFNβ induction in cells stimulated with synthetic dsRNA or infected with SARS-CoV-2, Zika virus or vesicular stomatitis virus (VSV). Similar findings of impaired IFNβ induction and antiviral gene expression were seen in PPP1R12C knockout cells, and in response to VSV infection, Ppp1r12c-deficient mice showed impaired innate immune responses, enhanced viral replication and higher mortality.

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  1. Nature Reviews Immunology http://www.nature.com/nri/

    Yvonne Bordon

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  1. Yvonne Bordon
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Correspondence to Yvonne Bordon.

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Bordon, Y. Disturbance of cytoskeleton primes RIG-I-like receptors. Nat Rev Immunol 22, 654–655 (2022). https://doi.org/10.1038/s41577-022-00789-y

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