Biology subjects

He, S.-Y.

Publications and source records attributed to He, S.-Y..

3 recordsLinked to original sources

bioRxiv2025

Actin Depolymerization Factors (ADFs) Moonlighting: Nuclear Immune Regulation by Interacting with WRKY Transcription Factors and Shaping the Transcriptome

Remodeling of the actin cytoskeleton is a critical process for plant immunity, essential for the transport, activation, and stabilization of immune-regulatory molecules and organelles. In this process, actin depolymerization factors (ADFs) function as key players through severing and depolymerizing actin microfilaments. However, recent evidence suggests that ADFs may possess non-canonical immune functions inside the nucleus, in addition to the canonic cytosolic role, a phenomenon not adequately explained by the traditional mechanistic model of ADF-actin dynamics. In this study, we demonstrate that Arabidopsis ADFs exhibit a moonlighting function in the nucleus, where they interact with transcriptional machinery to regulate the transcriptome during both the resting state and the immune responses. We show that ADF2/3/4 have redundant functions in defense against virulent and avirulent Pseudomonas syringae. Notably, it is nuclear - rather than cytosolic - ADFs that contribute to defense against P. syringae and mediate pro-immune transcription. Mechanistically, we demonstrate that nuclear ADFs interact with transcription factors, histone complexes, and other components of the transcriptional machinery. Specifically, ADF2/3/4 can form a complex with WRKY transcription factors, such as WRKY22/29/48, thereby directly regulating WRKY activity to shape the pro-immune transcriptome. In summary, our study reveals that ADFs moonlight as direct regulators of transcription factors, mediating a broad range of nuclear-cytoplasmic regulation in plant immunity and potentially other biological processes.

plant biology↗

bioRxiv2024

Transcriptional activation of Bmal1 drives the inflammatory activity of monocytes by modulating mitochondrial unfolded protein response during hypobaric hypoxic stress

BackgroundHypoxic stress-induced inflammation had been considered to play an important role in the onset and progression of altitude-related illnesses, but the origin of inflammatory cytokines, the specific responding cell types, and molecular mechanisms remain unknown. Mitochondria are responsible for oxygen consumption and recently reported to be the master regulators of inflammation, but it is not clear whether and how mitochondrial organelles sense the hypoxic stress and then control the inflammation. MethodsHuman subjects and mouse models were exposed to real or simulated altitude of 5500 m. Bone marrow-derived macrophages (BMDMs) and monocyte RAW264.7 cells were cultured under 1% oxygen hypoxic conditions. Myeloid-specific Bmal1 knock-out mice were generated by crossing Bmal1flox/flox mice with Lyz2-Cre mice. Inflammation was investigated by assessing inflammatory mediators, monocyte activities, and leukocyte infiltrating. Mitochondrial unfolded protein response was examined by measuring stress markers, such as LONP1, AFG3L2, and HSP60. The target molecular mechanisms were identified by performing bioinformatic analyses, ChIP assays, and gain/loss-of-function experiments. Results1) Monocytes in peripheral blood mononuclear cell (PBMCs) were more sensitive and contributed promptly to circulating inflammation in response to acute hypobaric hypoxia. 2) Hypoxic stress triggered the mitochondrial unfolded protein response and then induced the mito-inflammation (NLRP3 inflammasome) in monocytes. 3) Activation of Bmal1 drove mitochondrial stress and mito-inflammation by promoting Fis1-mediated mitochondrial fission in monocytes under hypoxia. 4) BHLHE40, a stress-responsive transcription factor directly targeted by HIF-1, stimulated Bmal1 transcription in monocytes under hypobaric hypoxia. 5) Myeloid-specific Bmal1 deletion alleviated systemic circulating and vascular inflammation under acute hypobaric hypoxia. ConclusionBHLHE40, a transcription factor associated with hypoxia, stimulated Bmal1, which in turn triggered the mitochondrial unfolded protein response and drove the mito-inflammation in monocytes by promoting Fis1-mediated mitochondrial fission. Our work provides a novel mechanism which may develop the circadian targeting drugs for altitude or hypoxia-related diseases.

molecular biology↗

bioRxiv2020

Oxicam-type nonsteroidal anti-inflammatory drugs inhibit NPR1-mediated salicylic acid pathway

Salicylic acid (SA) and its structural analogs are nonsteroidal anti-inflammatory drugs (NSAIDs) that target mammalian cyclooxygenases. In plants, SA acts as a defense hormone that regulates NON-EXPRESSOR OF PATHOGENESIS RELATED GENES 1 (NPR1), the master transcriptional regulator of immunity-related genes. We identified a number of NSAIDs that enhance bacterial effector-induced cell death. Among them, the oxicam-type NSAIDs tenoxicam (TNX), meloxicam, and piroxicam, but not other types of NSAIDs, exhibit an inhibitory effect on immunity to bacteria and SA-dependent immune responses in plants. TNX treatment reduces NPR1 levels, independently from the proposed SA receptors NPR3 and NPR4. Instead, TNX induces oxidation of cytosolic redox status, which is also affected by SA and regulates NPR1 homeostasis. Surprisingly, however, cysteine modification associated with NPR1 oligomerization via intermolecular disulfide bonds is not affected by either SA or TNX. Therefore, oxicam-type NSAIDs highlight importance of SA effects on the cytosolic redox status, but not on cysteine modification or oligomerization of NPR1.

plant biology↗