All Items
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Abstract:
Cells must eliminate various unwanted organelles to maintain homeostasis, yet how they achieve this when their primary degradation system, the lysosome, is impaired remains poorly understood. Here, we discover cytopurgosis, a lysosome-independent organelle-removal pathway that expels multiple organelles, including entire lysosomes, within large extracellular vesicles that we termed "purgasomes"....
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Abstract:
Historical records of wildlife are important information in understanding their historical distribution patterns and indigenous knowledge of wildlife in traditional cultures, and have significant academic value and practical implications for the conservation of wildlife. However, the complex system of animal names and numerous synonyms in historical documents often complicates the identification...
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Abstract:
The human Ether-a-go-go Related Gene (hERG)-encoded potassium channel is critical for cardiac ventricular action potential repolarization and serves as a core target for preclinical drug safety screening. The lack of stable, high-expression hERG cell models has limited the reliability and throughput of functional assays for hERG channel evaluation. Thus, developing a robust stable hERG-expressing...
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Abstract:
Antibody-dependent enhancement (ADE) of viral entry remains a mechanistically unresolved phenomenon in SARS-CoV-2 variants, with its variant-specificity and pathological consequences poorly defined. Through systematic profiling of 114 monoclonal antibodies (mAbs) across major variants of concern (VOCs), we discover that the Delta variant exhibits uniquely potent ADE mediated by mAbs targeting...
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Abstract:
The heteromeric KCNQ2/3 channel constitutes the molecular correlate of the neuronal M-current, a potassium conductance essential for stabilizing resting membrane potential and controlling neuronal excitability. Despite its physiological and therapeutic importance, the structural basis for its unique functional properties—distinct from homomeric KCNQ2 or KCNQ3—has remained enigmatic, and its...
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Abstract: Conserved TIR domain proteins play essential roles in immune signaling, development, and neurodegeneration. Here, we identify Raw as a member of a distinct TIR protein family that functions as a cADPR-specific hydrolase, with catalytic mutations phenocopying delayed axon degeneration. While Raw and dSarm synergistically deplete NAD to drive axon degeneration, they antagonistically regulate cADPR...
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Abstract: Helicobacter pylori (H. pylori) infection is a major driver of gastric diseases, but with a global prevalence of nearly 50%, precise risk stratification among infected individuals remains challenging. Here, we constructed a comprehensive H. pylori proteome microarray encompassing 1,631 proteins and applied it to screen sera from patients with chronic atrophic gastritis (CAG), providing a...
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Abstract:
Human M-channels, primarily assembled by heteromeric KCNQ2/KCNQ3 subunits, are critical regulators of neuronal excitability, and loss-of-function mutations in either subunit are linked to epileptic disorders. Yet, the molecular mechanisms underlying heteromeric assembly, gating, and pharmacological modulation have remained largely elusive. Here, we present high-resolution cryo-EM structures of...
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Abstract:
The M-channel, a heterotetrameric voltage-gated potassium channel formed by KCNQ2 and KCNQ3 subunits, critically regulates neuronal excitability, with dysfunction linked to epilepsy and developmental encephalopathies. Despite its physiological importance, structural mechanisms governing its unique heteromeric assembly and subthreshold gating have remained unresolved. We present cryo-EM structures...
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Abstract:
Cell morphology reflects cellular states, particularly cell fates with specific spatiotemporal features, like the spreading of epidermal cells in skin. However, how cell morphology relates to cell fate and genetic programs remains unclear. In this study, we leveraged the up-to-date lineage-resolved 3D cell morphology dataset of worm Caenorhabditis elegans embryogenesis. Twelve quantitative...