Person:
Zhao, Yun

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Zhao

First Name

Yun

Name

Zhao, Yun

Filters

2010 - 20142

Settings

Author's Publications: search.filters.isAuthorOfPublication.61d5a8fa-fbf8-42ec-9dde-1866871c374f

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    GEF-H1 controls microtubule-dependent sensing of nucleic acids for antiviral host defenses
    (2014) Chiang, Hao-Sen; Zhao, Yun; Song, Joo-Hye; Liu, Song; Wang, Ninghai; Terhorst, Cox; Sharpe, Arlene; Basavappa, Megha; Jeffrey, Kate; Reinecker, Hans-Christian
    Detailed understanding of the signaling intermediates that confer the sensing of intracellular viral nucleic acids for induction of type I interferons is critical for strategies to curtail viral mechanisms that impede innate immune defenses. Here we show that the activation of the microtubule-associated guanine nucleotide exchange factor GEF-H1, encoded by Arhgef2, is essential for sensing of foreign RNA by RIG-I-like receptors. Activation of GEF-H1 controls RIG-I and Mda5-dependent phosphorylation of IRF3 and induction of interferon-β expression in macrophages. Generation of Arhgef2−/− mice revealed a pronounced signaling defect that prevented antiviral host responses to encephalomyocarditis virus and influenza A virus. Microtubule networks sequester GEF-H1 that upon activation is released to enable antiviral signaling by intracellular nucleic acid detection pathways.
  • Thumbnail Image
    Publication
    Ablation of Whirlin Long Isoform Disrupts the USH2 Protein Complex and Causes Vision and Hearing Loss
    (Public Library of Science, 2010) Yang, Jun; Liu, Xiaoqing; Zhao, Yun; Adamian, Michael; Pawlyk, Basil; Sun, Xun; McMillan, D. Randy; Liberman, M.; Li, Tiansen
    Mutations in whirlin cause either Usher syndrome type II (USH2), a deafness-blindness disorder, or nonsyndromic deafness. The molecular basis for the variable disease expression is unknown. We show here that only the whirlin long isoform, distinct from a short isoform by virtue of having two N-terminal PDZ domains, is expressed in the retina. Both long and short isoforms are expressed in the inner ear. The N-terminal PDZ domains of the long whirlin isoform mediates the formation of a multi-protein complex that includes usherin and VLGR1, both of which are also implicated in USH2. We localized this USH2 protein complex to the periciliary membrane complex (PMC) in mouse photoreceptors that appears analogous to the frog periciliary ridge complex. The latter is proposed to play a role in photoreceptor protein trafficking through the connecting cilium. Mice carrying a targeted disruption near the N-terminus of whirlin manifest retinal and inner ear defects, reproducing the clinical features of human USH2 disease. This is in contrast to mice with mutations affecting the C-terminal portion of whirlin in which the phenotype is restricted to the inner ear. In mice lacking any one of the USH2 proteins, the normal localization of all USH2 proteins is disrupted, and there is evidence of protein destabilization. Taken together, our findings provide new insights into the pathogenic mechanism of Usher syndrome. First, the three USH2 proteins exist as an obligatory functional complex in vivo, and loss of one USH2 protein is functionally close to loss of all three. Second, defects in the three USH2 proteins share a common pathogenic process, i.e., disruption of the PMC. Third, whirlin mutations that ablate the N-terminal PDZ domains lead to Usher syndrome, but non-syndromic hearing loss will result if they are spared.