GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses

Hao-Sen Chiang, Yun Zhao, Joo-Hye Song, Song Liu, Ninghai Wang, Cox Terhorst, Arlene H Sharpe, Megha Basavappa, Kate L Jeffrey & Hans-Christian Reinecker, Nat Immunol. 2014 Jan;15(1):63-71.

Speaker: Wei-Jheng Hunag (黃偉政)                Time: 13:00~14:00, Feb 26, 2014

Commentator: Dr. Chih-Peng Chang (張志鵬 老師)   Place: Room 601

Abstract

The two major components of the cellular cytoskeleton, actin and microtubules, are dynamically coupled to regulate a variety of physiological and pathological cell functions (1). Many viruses utilize the dynein-based transport system for replication and intracellular movement along microtubules (2), but the roles of microtubule-based trafficking in the innate immunity remains unknown. Microtubule-associated guanine nucleotide exchange factor H1 (GEF-H1), encoded by the arhgef2, was originally identified as an oncoprotein member of the Dbl family that is sequestered on microtubules and directs spatiotemporal activation of Rho GTPases. In this study, the authors found that GEF-H1 was required in 5’-ppp dsRNA-induced, RIG-I–like receptors (RLRs)-mediated, interferon (IFN) and proinflammatory cytokines production. GEF-H1 facilitates TBK1-mediated IRF3 activation in a microtubule-dependent manner. In the presence of nocodazole, they found a functional microtubule network was required for the IFN induction and the interaction between GEF-H1 and TBK1. Activation of GEF-H1 by dephosphorylation and released from microtubule are required for the RLR signaling and amplification of innate immune response. Finally, authors showed GEF-H1 is required in the innate immunity against Influenza A and Encephalomyocarditisvirus. Take together, this study demonstrated GEF-H1 mediates the induction of antiviral host defenses by cytosolic receptors RIG-I and Mda5 in macrophages.

Reference

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